US5972710A - Microfabricated diffusion-based chemical sensor - Google Patents
Microfabricated diffusion-based chemical sensor Download PDFInfo
- Publication number
- US5972710A US5972710A US08/829,679 US82967997A US5972710A US 5972710 A US5972710 A US 5972710A US 82967997 A US82967997 A US 82967997A US 5972710 A US5972710 A US 5972710A
- Authority
- US
- United States
- Prior art keywords
- stream
- laminar flow
- channel
- flow channel
- particles
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/30—Injector mixers
- B01F25/31—Injector mixers in conduits or tubes through which the main component flows
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/30—Micromixers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/30—Micromixers
- B01F33/3039—Micromixers with mixing achieved by diffusion between layers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
- B01L3/502776—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for focusing or laminating flows
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/0005—Field flow fractionation
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00819—Materials of construction
- B01J2219/00824—Ceramic
- B01J2219/00828—Silicon wafers or plates
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00819—Materials of construction
- B01J2219/00831—Glass
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/0095—Control aspects
- B01J2219/00952—Sensing operations
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0636—Focussing flows, e.g. to laminate flows
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0654—Lenses; Optical fibres
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/087—Multiple sequential chambers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
- B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Electro-optical investigation, e.g. flow cytometers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/38—Flow patterns
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/60—Construction of the column
- G01N30/6095—Micromachined or nanomachined, e.g. micro- or nanosize
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
- G01N35/085—Flow Injection Analysis
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S366/00—Agitating
- Y10S366/01—Micromixers: continuous laminar flow with laminar boundary mixing in the linear direction parallel to the fluid propagation with or without conduit geometry influences from the pathway
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
- Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
- Y10T436/2575—Volumetric liquid transfer
Definitions
- This invention relates generally to microsensors and methods for analyzing the presence and concentration of small particles in streams containing both these small particles and larger particles by diffusion principles.
- the invention is useful, for example, for analyzing blood to detect the presence of small particles such as hydrogen, sodium or calcium ions in a stream containing cells.
- a similar arrangement can be used to separate particles. Consider a mixture of particles of two different sizes suspended in water in one box and pure water in the other. If the demon opens and closes the door between the boxes quickly enough so that none of the larger particles have time to diffuse through the doorway, but long enough so that some of the smaller particles have enough time to diffuse into the other box, some separation will be achieved.
- Diffusion is a process which can easily be neglected at large scales, but rapidly becomes important at the microscale.
- D the diffusion coefficient of the molecule.
- diffusion is relatively slow at the macro-scale (e.g. hemoglobin with D equal to 7 ⁇ 10 -7 cm 2 /s in water at room temperature takes about 106 seconds (ten days) to diffuse across a one centimeter pipe, but about one second to diffuse across a ten micron channel).
- a process called “field-flow fractionation” has been used to separate and analyze components of a single input stream in a system not made on the microscale, but having channels small enough to produce laminar flow.
- Various fields, including concentration gradients are used to produce a force perpendicular to the direction of flow to cause separation of particles in the input stream. See, e.g. Giddings, J. C., U.S. Pat. No. 3,449,938, Jun. 17, 1969, “Method for Separating and Detecting Fluid Materials;” Giddings, J. C., U.S. Pat. No. 4,147,621, Apr. 3, 1979, “Method and Apparatus for Flow Field-Flow Fractionation;” Giddings, J.
- SPLITT Split Flow Thin Cell
- Microfluidic devices allow one to take advantage of diffusion as a rapid separation mechanism.
- Flow behavior in microstructures differs significantly from that in the macroscopic world. Due to extremely small inertial forces in such structures, practically all flow in microstructures is laminar. This allows the movement of different layers of fluid and particles next to each other in a channel without any mixing other than diffusion.
- diffusion is a powerful tool to separate molecules and small particles according to their diffusion coefficients, which is usually a function of their size.
- This invention provides a channel cell system for detecting the presence of analyte particles in a sample stream also comprising larger particles comprising:
- said indicator stream preferably comprising an indicator substance, for example, a pH-sensitive dye, which indicates the presence of said analyte particles by a detectable change in property when contacted with said analyte particles, and (2) said sample stream;
- said laminar flow channel has a depth sufficiently small to allow laminar flow of said streams adjacent to each other and a length sufficient to allow analyte particles to diffuse into said indicator stream to the substantial exclusion of said larger particles in said sample stream to form a detection area;
- outlet means for conducting said streams out of said laminar flow channel to form a single mixed stream.
- a single indicator stream and a single sample stream are used; however, the methods and devices of this invention may also use multiple sample and/or indicator streams, and reference or calibration streams, all in laminar flow with each other.
- liquid connections means that fluid flows between the two or more elements which are in fluid connection with each other.
- detection means determination that a particular substance is present. Typically, the concentration of a particular substance is determined.
- the methods and apparatuses of this invention can be used to determine the concentration of a substance in a sample stream.
- the channel cell system of this invention may comprise external detecting means for detecting changes in an indicator substance carried within the indicator stream as a result of contact with analyte particles. Detection and analysis is done by any means known to the art, including optical means, such as optical spectroscopy, and other means such as absorption spectroscopy or fluorescence, by chemical indicators which change color or other properties when exposed to the analyte, by immunological means, electrical means, e.g.
- Electrodes inserted into the device electrochemical means, radioactive means, or virtually any microanalytical technique known to the art including magnetic resonance techniques, or other means known to the art to detect the presence of an analyte such as an ion, molecule, polymer, virus, DNA sequence, antigen, microorganism or other factor.
- an analyte such as an ion, molecule, polymer, virus, DNA sequence, antigen, microorganism or other factor.
- optical or fluorescent means are used, and antibodies, DNA sequences and the like are attached to fluorescent markers.
- particles refers to any particulate material including molecules, cells, suspended and dissolved particles, ions and atoms.
- the input stream may be any stream containing particles of the same or different size, for example blood or other body fluid, contaminated drinking water, contaminated organic solvents, urine, biotechnological process samples, e.g. fermentation broths, and the like.
- the analyte may be any smaller particle in the input stream which is capable of diffusing into the indicator stream in the device, e.g. hydrogen, calcium or sodium ions, proteins, e.g. albumin, organic molecules, drugs, pesticides, and other particles.
- small ions such as hydrogen and sodium diffuse rapidly across the channel, whereas larger particles such as those of large proteins, blood cells, etc. diffuse slowly.
- the analyte particles are no larger than about 3 micrometers, more preferably no larger than about 0.5 micrometers, or are no larger than about 1,000,000 MW, and more preferably no larger than about 50,000 MW.
- the system may also include an indicator stream introduced into one of the inlet means comprising a liquid carrier containing substrate particles such as polymers or beads having an indicator substance immobilized thereon.
- the system may also include an analyte stream comprising substrate particles such as polymer beads, antibodies and the like on which an indicator substance is immobilized.
- the liquid carrier can be any fluid capable of accepting particles diffusing from the feed stream and containing an indicator substance.
- Preferred indicator streams comprise water and isotonic solutions such as salt water with a salt concentration of about 10 mM NaCl, KCl or MgCl, or organic solvents like acetone, isopropyl alcohol, ethanol, or any other liquid convenient which does not interfere with the effect of the analyte on the indicator substance or detection means.
- the channel cell may be fabricated by microfabrication methods known to the art, e.g. as exemplified herein, a method comprising forming channels in a silicon microchip, such as by etching grooves into the surface of the silicon microchip and placing a glass cover over the surface. Precision injection molded plastics may also be used for fabrication.
- the method of this invention is designed to be carried out such that all flow is laminar. In general, this is achieved in a device comprising microchannels of a size such that the Reynolds number for flow within the channel is below about 1, preferably below about 0.1. Reynolds number is the ratio of inertia to viscosity. Low Reynolds number means that inertia is essentially negligible, turbulence is essentially negligible, and, the flow of the two adjacent streams is laminar, i.e. the streams do not mix except for the diffusion of particles as described above. Flow can be laminar with Reynolds number greater than 1. However, such systems are prone to developing turbulence when the flow pattern is disturbed, e.g., when the flow speed of a stream is changed, or when the viscosity of a stream is changed.
- the laminar flow channel is long enough to permit small analyte particles to diffuse from the sample stream and have a detectable effect on an indicator substance or detection means, preferably at least about 2 mm long.
- the length of the flow channel depends on its geometry.
- the flow channel can be straight or curved in any of a number of ways.
- the flow channel can include one or more "hairpin turns," making a tight stairstep geometry.
- the flow channel can be in the shape of a coil, like a neatly wound up garden hose.
- Non-straight channel geometries allow for increasing the length of the flow channel without increasing the size/diameter of the substrate plate in which the channel is formed, e.g., a silicon microchip.
- the diffusion coefficient of the analyte which is usually inversely proportional to the size of the analyte, affects the desired flow channel length. For a given flow speed, particles with smaller diffusion coefficients require a longer flow channel to have time to diffuse into the indicator stream.
- the flow rate can be decreased.
- the flow rate is achieved by a pumping means or pressure source, some of which cannot produce as low a pressure and flow rate as may be desired, to allow enough time for diffusion of particles with small diffusion coefficients.
- the flow rate is slow enough and some particles are of significantly different density from the surrounding fluid streams, particles denser than the surrounding fluid streams may sink to the bottom of the flow channel and particles less dense than the surrounding fluid streams may float to the top of the flow channel. It is preferable that the flow rate be fast enough that hydrodynamic forces substantially prevent particles from sticking to the bottom, top, or walls of the flow channel.
- a small change in pressure leads to larger errors in measurement accuracy at lower flow rates.
- other factors such as changes in viscosity of fluids, can lead to larger errors in measurement accuracy.
- the flow channel can be straight or non-straight, i.e., convoluted.
- a convoluted flow channel as used herein refers to a flow channel which is not straight.
- a convoluted channel can be, for example, coiled in a spiral shape or comprise one or a plurality of "hairpin" curves, yielding a square wave shape. Convoluted channels provide longer distances for diffusion to occur, thereby allowing for measurement of analytes with larger diffusion coefficients, e.g., typically larger analytes.
- the channel length of a straight flow channel is between about 5 mm and about 50 mm.
- the length of the flow channel is defined or limited only by the size of the microchip or other substrate plate into which the channel is etched or otherwise formed.
- the channel width (diffusion direction) is preferably between about 20 micrometers and about 1 mm.
- the channel is more preferably made relatively wide, e.g. at least about 200 micrometers, which makes it easier to measure indicator fluorescence with simple optics, and less likely for particles to clog the channel.
- the channel can be made as narrow as possible while avoiding clogging the channel with the particles being used. Narrowing the width of the channel makes diffusion occur more rapidly, and thus detection can be done more rapidly.
- the channel depth is small enough to allow laminar flow of two streams therein, preferably no greater than about 1000 micrometers and more preferably between about 50 micrometers and about 400 micrometers.
- the laminar flow channel may be long enough to allow the indicator and sample streams to reach equilibrium with respect to the analyte particles within the channel. Equilibrium occurs when the maximum amount of smaller particles have diffused into the indicator stream.
- the system may also comprise specimen channel and outlet means such as smaller channels for conducting specimen streams from the indicator stream at successive intervals along the length of the laminar flow channel, and means including viewports and fluorescence detectors for measuring changes in an indicator substance in each specimen stream, whereby concentration of the analyte in the sample stream may be determined.
- specimen channel and outlet means such as smaller channels for conducting specimen streams from the indicator stream at successive intervals along the length of the laminar flow channel, and means including viewports and fluorescence detectors for measuring changes in an indicator substance in each specimen stream, whereby concentration of the analyte in the sample stream may be determined.
- Dual detection embodiments of the device of the present invention which allow for detection of both undissolved and dissolved analytes are also provided. Detection of both undissolved and dissolved analytes can be achieved in one dual detection device: dissolved particles can be detected in the flow channel of the T-sensor and undissolved particles can be detected in a v-groove channel or sheath flow module, either or both of which can be in fluid connection with a T-sensor flow channel. Branching flow channels can provide for fluid connection between a T-sensor flow channel and a v-groove channel and/or sheath flow module.
- the channel cell systems of this invention can be in fluid connection with a v-groove flow channel, which preferably has a width at the top small enough to force the particles into single file but large enough to pass the largest particles without clogging.
- V-groove channels are formed by anisotropic EPW (ethylenediamine-pyrocatechol-water) etching of single crystalline silicon microchips, providing access to reflective surfaces with precisely etched angles relative to the surface of the microchip (Petersen, Proc. IEEE 70 (5): 420-457, 1982).
- EPW ethylenediamine-pyrocatechol-water
- detectors placed at small and large angles with respect to the portion of the probe beam reflected from the v-groove wall can be used to count particles, such as cells, and distinguish them by size (via small angle detector) and structure/morphology (via large angle detector).
- an appropriate laser or LED source e.g., a blue laser, which can be determined by routine choice by those of ordinary skill in the art, fluorescence detection can be performed by placing an appropriate filter in front of the large angle detector.
- the flow channel of the T-sensor can be in fluid connection with a v-groove channel allowing for dual detection of dissolved and undissolved, single-file particles with one device.
- the fluid streams can flow first through a T-sensor flow channel and then through a v-groove channel, via branching flow channels.
- the fluid stream can flow first through a v-groove channel and then through a T-sensor flow channel.
- the sheath flow module includes a first plate of material having formed therein a laminar fluid flow channel; at least two inlets, each inlet joining the laminar flow channel at a junction, the first inlet junction being wider than the second inlet junction, and an outlet from the flow channel.
- a second plate e.g., a transparent cover plate, seals the module and allows for optical measurements.
- a transparent cover plate allows for optical measurements by reflection, in cases where the first plate is a reflective material, e.g., silicon.
- a first inlet allows for introduction of a first fluid into the flow channel.
- the first fluid is the sheath fluid.
- a second inlet allows for introduction of a second fluid into the sheath fluid while it is flowing through the flow channel.
- the second fluid is the center fluid. Because the second inlet junction is narrower than the first inlet junction, the center fluid becomes surrounded on both sides by the sheath fluid.
- the depth of the flow channel can be decreased, leading to vertical hydrodynamic focusing.
- the width of the flow channel can be decreased, leading to horizontal hydrodynamic focusing. The decrease in depth and width can be gradual or abrupt. Hydrodynamic focusing in the sheath flow module leads to single file particle flow.
- the sheath flow module can be in fluid connection with the channel cell system of the present invention.
- the fluid streams can flow first through a T-sensor flow channel and then through a sheath flow module.
- the fluid stream can flow first through a sheath flow module and then through a T-sensor flow channel.
- the channel cell system of a preferred embodiment of this invention comprises channel grooves in the form of a "T” or a "Y” having a central trunk and two branches etched into the surface of a silicon microchip, which surface is thereafter covered with a glass sheet.
- the central groove is formed of the trunk of the "T” or "Y”, and the branches are the inlet means in fluid connection with the laminar flow channel for respectively conducting the sample and indicator streams into the laminar flow channel.
- Channel cells of this invention may also include multiple inlet branches in fluid connection with the laminar flow channel for conducting a plurality of inlet streams into said channel. These may be arranged in a "candelabra"--like array or may be arranged successively along a "crossbar” for the "T” or the branches of the "Y” configuration, the only constraint being that laminar flow of all the streams must be preserved.
- Inlet means include the inlet channels or “branches” and may also include other means such as tubes, syringes, and the like which provide means for injecting feed fluid into the device.
- Outlet means include collection ports, and/or means for removing fluid from the outlet, including receptacles for the fluid, means inducing flow by capillary action, pressure, gravity, and other means known to the art. Such receptacles may be part of an analytical or detection device.
- the channel cell system transects the width of the substrate plate in which the channel cell system is formed.
- Substrate plate refers to the piece of material in which the channel cell system of this invention is formed, e.g., a silicon wafer and a plastic sheet.
- the analyte detection area, and optionally other parts of the channel cell system lie between optically transparent plates in a space which cuts through the entire width of the substrate plate.
- Analyte detection area as used herein refers to that portion of the indicator stream where analyte particles create a detectable change in the indicator stream.
- Optical measurements exploiting reflected light are referred to herein as detection by reflection, whereas optical measurements exploiting transmitted light are referred to herein as detection by transmission.
- a method for detecting the presence of analyte particles in a sample stream, preferably a liquid stream, also comprising larger particles comprising:
- said indicator stream preferably comprising an indicator substance which indicates the presence of said analyte particles, by a detectable change in property when contacted with particles of said analyte into said laminar flow channel, whereby said sample stream and said indicator stream flow in adjacent laminar streams in said channel;
- the flow rate of the input streams is preferably between about 5 micrometers/second and about 5000 micrometers/second, more preferably about 25 micrometers/second. Preferably the flow rate for both streams is the same.
- the method and system of this invention include determining the concentration of the analyte particles in the sample stream by detecting the position within the laminar flow channel of analyte particles from the sample stream diffusing into the indicator stream causing a detectable change in the indicator stream or in an indicator substance in the indicator stream.
- the sample stream and the indicator stream may be allowed to reach equilibrium within the laminar flow channel.
- the location of the boundary of the detection area i.e. that portion of the indicator stream containing diffused particles at a detectable concentration
- the unaffected indicator stream may be used to provide information about flow speed and/or sample concentration.
- the physical location of this boundary in the channel for a given analyte stays the same over time as long as the flow speed is constant and the sample unchanged.
- the location and size of the detection area can be varied by varying flow rate, sample concentration, and/or concentration of an indicator substance so as to optimize the signal for detection.
- Information useful for determining the concentration of the analyte particles in the sample stream may be obtained by providing means for conducting specimen streams from the indicator stream at successive intervals along the length of the laminar flow channel, such as smaller channels equipped with viewports as described herein. Detection means such as those listed above are used to measure signals from the indicator stream. Changes in the intensity of the signals from specimen channel to specimen channel may be used to calculate the concentration of analyte particles in the original sample.
- the method of one embodiment of this invention includes the use of an indicator substance which is immobilized on a particulate substrate carried within the indicator stream.
- the indicator substance is preferably a substance which changes in fluorescence or color in the presence of analyte particles, such as a dye, enzymes, and other organic molecules that change properties as a function of analyte concentration.
- analyte particles such as a dye, enzymes, and other organic molecules that change properties as a function of analyte concentration.
- indicator substance is also used to refer to polymeric beads, antibodies or the like having dyes or other indicators immobilized thereon. It is not necessary that the indicator stream comprise an indicator substance when detection means such as those directly detecting electrical, chemical or other changes in the indicator stream caused by the analyte particles are used.
- analytes can be determined optically in turbid and strongly colored solutions such as blood, without the need for prior filtering or centrifugation; cross-sensitivities of indicator dyes to larger sample components (a common problem) can be avoided; and the indicator can be kept in a solution in which it displays its optimal characteristics (e. g., cross-sensitivities to pH or ionic strength can be suppressed by using strongly buffered solutions).
- Measurements of the indicator stream at several locations along the channel can compensate for some remaining cross-sensitivities.
- the flow channel can be wide, which makes it easy to measure the indicator fluorescence with simple optics.
- the system is less subject to biofouling and clogging than membrane systems.
- the system is also tunable in that sample or indicator stream concentrations and/or flow rates can be varied to optimize the signal being detected. For example, if a reaction takes about five seconds, the system can be adjusted so that the reaction will be seen in the central portion of the device.
- the method can be conducted by a continuous flow-through of sample and indicator streams.
- the steady-state nature of this method makes longer signal integration times possible.
- the sample stream may contain particles larger than the analyte particles which are also sensitive to the indicator substance. These do not diffuse into the indicator stream and thus do not interfere with detection of the analyte.
- a method for determining kinetic rate constants as a function of distance traveled by the sample stream and indicator stream from the T-joint where the two streams meet is provided.
- kinetic measurements are made by plotting a physical property related to concentration versus time, i.e., time of reaction.
- the method provided herein for making kinetic measurements as a function of distance traveled by the sample and indicator stream, rather than as a function of time, is advantageous for the following reasons.
- the constituents of the streams, i.e., the particles, and the concentrations thereof, at a given position in the flow channel remain constant, given that the flow rate is constant.
- This method allows for integrating the data from detection, e.g., optical measurements, over time, thereby increasing the accuracy of the data collected and hence of the calculated/determined rate constants. Furthermore, if an experimental error occurs during detection, e.g. in the collection of data, at a given time, one can merely perform the detection measurement again, at the distance/position in the flow channel where the error occurred. In prior art methods of making kinetic measurements, if data at a given time point are lost due to experimental error, those data cannot be collected again during the same experiment.
- FIG. 1 is a schematic representation of flow and diffusion within the T-sensor channel cell embodiment of this invention.
- FIG. 2 is a fluorescence micrograph of a T-sensor of this invention in which a buffer solution of pH 9 (right inlet) is flowing into the device, and a weakly buffered indicator dye solution (pH 5) enters from the left. The distinct conversion of the dye from one form to the other as diffusion proceeds is clearly visible.
- FIG. 3 shows the layout of the viewport-T-sensor embodiment of this invention.
- the indicator stream comes from the right T-leg, and is a solution of indicator dye in a low ionic strength buffer of pH 9.
- the sample stream, which is introduced from the left, here is a 0.15M buffer solution of pH 5.
- Several portions of the indicator stream which contains the indicator dye are continuously taken out of the channel as specimen streams at various locations.
- FIG. 4 shows a v-groove flow channel coupled with a flow cytometer optical head.
- FIG. 5 shows a convoluted flow channel in a square wave shape.
- FIG. 6 shows a convoluted flow channel in a coiled shape.
- FIG. 7A shows a T-sensor with a rounded T-joint.
- FIG. 7B shows a viewport-T-sensor with a rounded T-joint.
- FIG. 8 shows a convoluted flow channel with a plurality of detection areas for making kinetic measurements as a function of distance.
- FIG. 9, comprising FIGS. 9A-9C, shows embodiments with branching flow channels for dual detection of both dissolved and undissolved analytes.
- FIG. 10 comprising FIGS. 10A-10C, shows a sheath flow module.
- FIG. 11 shows a T-sensor in which the analyte detection area is etched all the way through the width of the substrate plate.
- microscale channel cells of this invention are useful to separate smaller particles from larger particles in a sample stream based on the fact that the diffusion coefficient of a particle is substantially inversely proportional to the size of the particle so that larger particles diffuse more slowly than smaller particles, on the fact that diffusion occurs more quickly at the microscale of this invention than in larger scale separation devices known to the art and on the fact that laminar, non-turbulent flow can be induced in adjacent streams at the microscale.
- a channel cell in the form of a "T” is provided, referred to herein as T-sensor 10.
- the device can be microfabricated by etching on a silicon microchip.
- the geometry need not necessarily be a "T,” as a “Y.” Any angle that can be fabricated will also suffice.
- sample containing small molecules of interest, sample stream 80 is brought into the device through sample stream inlet port 30, from whence it flows into sample stream inlet channel 50, where it is referred to as sample inlet stream 55.
- An indicator stream 70 is brought into indicator stream inlet port 20, from whence it flows into indicator stream inlet channel 40, where it is referred to as indicator inlet stream 45.
- Sample inlet stream 55 meets indicator inlet stream 45 at T-joint 58 at the beginning of flow channel 100, and the two streams flow in parallel laminar flow as indicator stream 70 and sample stream 80 to exit port 60.
- the indicator stream 70 contains an indicator substance such as a dye which reacts with analyte particles in the sample stream 80 by a detectable change in physical properties. Indicator stream 70 is shown in white in FIG. 1. Due to the low Reynolds number in the small flow channel 100, no turbulence-induced mixing occurs and the two streams flow parallel to each other without mixing.
- sample components (analyte particles) diffuse to the left into indicator stream 70 and eventually become uniformly distributed across the width of flow channel 100 at uniform analyte particle diffusion area 120.
- the indicator stream 70 flows into flow channel 100 to form an initial reference area 85 into which analyte particles have not yet diffused.
- Analyte particles from sample stream 80 diffusing into indicator stream 70 form an analyte detection area 90 where analyte particles create a detectable change in the indicator stream 70, preferably by causing a detectable change in property in an indicator substance within the indicator stream 70.
- Particles of an indicator substance, e.g. dye particles may also diffuse into sample stream 80 to form a diffused indicator area 110. If this change in local concentration of the indicator substance is a problem in some applications, its diffusion rate can be made arbitrarily small by immobilization on polymers or beads, e.g. indicator beads 130.
- a sample stream 80 e.g. blood
- an indicator stream 70 containing an indicator dye are joined at the intersection of sample stream inlet channel 50 and indicator stream inlet channel 40, with flow channel 100 (i.e., T-joint 58) and flow laminarly next to each other in flow channel 100 until they exit the structure at exit port 60.
- Small ions such as H + and Na + diffuse rapidly across the diameter of flow channel 100, whereas larger ions such as the dye anion diffuse only slowly. Larger particles such as sugars, proteins, and the like and blood cells show no significant diffusion within the time the indicator stream 70 and sample stream 80 are in contact with each other.
- a front or detection area boundary 95 of indicator dye color or fluorescence change exists as diffusion proceeds up the channel to form detection area 90.
- detection area boundary 95 and reference area 85 may form a curved line best seen in FIG. 2.
- the location and curvature of the front can have its "resting location" adjusted by changing flow speed and channel width to optimize signal size and intensity.
- Analyte concentration is determined either by monitoring indicator signal at uniform analyte particle diffusion area 120 after substantial equilibration, or by noting the position of the front of steepest indicator color change, for example with a multi-element detector (see FIG. 3).
- the analyte detection area 90 can be as large as necessary to provide a detectable indicator signal.
- reference area 85 can be made to be as large as necessary to provide a detectable reference signal. Adjustments of these areas can be made as described below based on the diffusion coefficients of the analyte and indicator substance, flow rates and channel sizes.
- FIG. 2 shows a fluorescence microscope photograph of the T-sensor of FIG. 1 featuring an indicator inlet stream 45 which is a weakly buffered indicator dye solution of pH 5, and a sample inlet stream 55 which is a buffer solution of pH 9.
- the bright zone at the right is light reflecting on the silicon and does not relate to the sample and indicator streams.
- the sample stream 80 appears as a dark clear fluid on the right.
- the bright zone on the left is reference area 85 where analyte particles have not yet diffused into indicator stream 70.
- the grey area in the middle is analyte detection area 90 where OH - ions from the sample stream 80 have diffused into indicator stream 70 to form detection area 90.
- the fuzzy right edge of the grey detection area 90 is caused by dye particles diffusing into the sample stream 80. Uniform analyte particle diffusion area is shown at 120 where the OH - ions are uniformly diffused. The strongest signal is in the middle of detection area 90.
- FIG. 3 shows another embodiment of the T-sensor channel cell device of this invention having multiple specimen channels and viewports spaced along the length of the flow channel.
- an indicator inlet stream 45 enters from the right (rather than the left as in FIGS. 1 and 2) at indicator stream inlet port 20.
- a solution of indicator dye in a low ionic strength buffer of pH 9 is used.
- a sample inlet stream 55 which is a 0.15 M buffer solution of pH 5, enters from the left at sample stream inlet port 30.
- the concentration of the dye is only about 10% of the dye concentration used in FIG. 2.
- the indicator and sample streams 45 and 55 respectively, flow along indicator stream inlet channel and sample stream inlet channel 40 and 50 respectively, to meet at T-joint 58 and flow laminarly together along flow channel 100.
- Specimen streams 145 from indicator stream 70 which contain the indicator dye are continuously taken out of flow channel 100 at various locations. These specimen streams 145 flow through widenings which serve as viewports 140. Due to the size of the viewports 140 (several square millimeters), the fluorescence intensity can be easily monitored through a fluorescence microscope, or directly with a photodetector.
- the viewport closest to T-joint 58 contains mainly undisturbed dye solution, whereas the viewport closest to exit port 60 contains the sample stream 80 completely equilibrated with the indicator stream 70.
- the viewports in between contain the indicator stream 70 in various degrees of equilibration with the sample components. The closer to T-joint 58, the more likely the viewport is to contain only small ions from the sample.
- a fluorescence micrograph of the viewports shows that the color in the viewport closest to T-joint 58 is the red color of the base form of the undisturbed indicator dye, whereas the yellow-green color of the viewports closest to exit port 60 represent the acid form of the dye, after the pH of the indicator stream 70 was altered from basic to acidic when diffusion-based equilibration has been reached.
- the viewport T-sensor of FIG. 3 lends itself to simple referencing techniques.
- the integral fluorescence intensity of each viewport at one or more wavelengths can easily be measured through a fluorescence microscope, or directly, with photodiodes.
- the intensity ratio between selected viewports gives a measurement value largely independent of dye concentration and excitation light intensity. Measuring at more than one viewport increases the redundancy and therefore the measurement accuracy.
- this interference can be referenced out by comparing the ratios of the different viewports.
- the viewports closer to T-joint 58 will contain mainly smaller sample components, whereas the viewports further up flow channel 100 will also contain larger particles.
- the T-sensor device of the present invention can be used with reporter beads to measure pH, oxygen saturation and ion content, in biological fluids.
- reporter beads can also be used to detect and measure alcohols, pesticides, organic salts such as lactate, sugars such as glucose, heavy metals, and drugs such as salicylic acid, halothane and narcotics.
- Each reporter bead comprises a substrate bead having a plurality of at least one type of fluorescent reporter molecules immobilized thereon. Plurality as used herein refers to more than one.
- a fluorescent property of the reporter bead such as intensity, lifetime or wavelength, is sensitive to a corresponding analyte.
- Reporter beads are added to a fluid sample and the analyte concentration is determined by measuring fluorescence of individual beads, for example, in a flow cytometer. Alternatively, absorptive reporter molecules, which change absorbance as a function of analyte concentration, can be employed.
- the use of reporter beads allows for a plurality of analytes to be measured simultaneously, and for biological cells, the cell content can also be measured simultaneously. A plurality of analytes can be measured simultaneously because the beads can be tagged with different reporter molecules.
- the fluorescent reporter molecules of this invention can be any fluorescent molecules having fluorescence properties which are a function of the concentration of a particular analyte or class of analytes.
- Many dyes and fluorochromes known in the art can be used as reporter molecules in this invention (see, for example, R. P. Haugland, Handbook of Fluorescent Probes and Research Chemicals, 5th Edition, Molecular Probes Inc., Eugene, 1992).
- the criteria for reporter molecule selection are that the molecules can be immobilized on a substrate bead and that their fluorescence is a function of the concentration of an analyte.
- the reporter beads of U.S. patent application Ser. No. 08/621,170 are not required to have an immunoreagent, such as a ligan, antiligand, antigen or antibody, on the surface in combination with the reporter molecules.
- Fluorescent reporter molecules interact with the analyte in a way that changes the fluorescent properties of the reporter molecule.
- the reporter molecule reacts with the analyte, as in the case of albumin detection by AB 580 (Molecular Probes).
- the interaction is not a chemical reaction.
- the reporter molecule fluorescence can be quenched by nonradiative energy transfer to the analyte, as in the case of O 2 detection by ruthenium diphenyl phenanthroline.
- the fluorescence is sensitive to polarity changes in the fluid, which can be used to detect organic solvents and hydrocarbons within an aqueous fluid.
- the interaction can also be through other solvent effects, wherein the ionic strength of the solvent affects the fluorescence. Solvent effects can be used to determine the total concentration of all dissolved ions.
- the interaction can be a ligand/antiligand or antigen/antibody reaction.
- the interaction preferably does not lead to an aggregate with other particles and, in particular, does not create an aggregate containing a plurality of reporter beads. It is preferred that the interaction of the analyte with the reporter molecules does not significantly perturb the analyte concentration in the fluid.
- At least one fluorescence property of the reporter molecules is a function of analyte concentration.
- the property measured for the reporter beads can be any property which is affected by the analyte interaction with the beads, such as the fluorescence intensity, decay time or spectrum.
- the reporter molecules can be absorption indicators, for example the physiological pH indicator N9 (Merck, Germany) immobilized on a substrate bead. Such indicators change their absorption as a function of analyte concentration. Typically the color of the molecules changes (i.e., the wavelength of their absorption maximum changes).
- absorption indicators for example the physiological pH indicator N9 (Merck, Germany) immobilized on a substrate bead. Such indicators change their absorption as a function of analyte concentration. Typically the color of the molecules changes (i.e., the wavelength of their absorption maximum changes).
- Absorptive reporter molecules can be used in combination with fluorescent reporter molecules on a substrate bead, and absorptive beads can be used in combination with fluorescent beads.
- the substrate bead function is to allow the detection of an analyte, and optionally its concentration, with optical measurements of single beads.
- More than one type of reporter bead i.e., beads with different reporter molecules immobilized thereon, can be used to analyze a given sample, provided that the bead type can be identified.
- Beads can be identified by various means, including means employing bead size, e.g., light scattering; fluorescent tag(s) attached to the bead which has a different excitation and/or emission wavelength from that of the fluorescent reporter molecule attached to that bead; or by directly identifying the fluorescent molecule attached to the bead. This allows for detection of more than one analyte at a time.
- the substrate bead also functions to immobilize the reporter molecules to prevent their diffusion into the sample stream.
- the reporter molecules can be on the surface of or within the substrate bead.
- the beads can be fabricated from a variety of materials and can have any shape, not limited to spherical. Suitable materials include glass, latex, hydrogels, polystyrene and liposomes.
- the beads can have added surface groups to facilitate attaching reporter molecules, such as carboxyl groups on latex and amino-modified polystyrene.
- Adsorption based coatings can be prepared by immersing the substrate beads in a reporter molecule solution and then washing off excess reporter molecules. Reporter molecules can similarly be diffused into the cavity of controlled pore glass beads. Reporter molecules can also be covalently immobilized by chemically attaching them to functional groups of suitable substrate beads. Polymerized beads can be formed in a solution containing reporter molecules, thereby trapping the molecules in a fixed polymer cavity.
- lipids can be mixed with a reporter molecule solution, the solution shaken, and the liposomes separated.
- the beads are mixed with a fluid sample and the fluorescence or absorption of individual beads is measured.
- the beads can be dry before mixing with the sample or can be dispersed in a fluid.
- the added volume of beads and any accompanying fluid be small compared to the sample volume (for example ⁇ 1%) so that sample dilution is insignificant.
- the channel cells of this invention may be formed by any techniques known to the art, preferably by etching the flow channels onto the horizontal surface of a silicon microchip and placing a lid, preferably of an optically clear material such as glass or a silicone rubber sheet, on the etched substrate.
- Other means for manufacturing the channel cells of this invention include using silicon structures or other materials as a template for molding the device in plastic, micromachining, and other techniques known to the art. The use of precision injection molded plastics to form the devices is also contemplated. Microfabrication techniques are known to the art, and more particularly described below.
- channel cells of this invention have hydrophilic surfaces to facilitate flow of liquid therein and allow operation of the device without the necessity for pressurization.
- the substrate may be treated by means known to the art following fabrication of the channels, to render it hydrophilic.
- the lid is also preferably treated to render it hydrophilic.
- the T-sensor channel system of this invention can be in fluid connection with one or more v-groove channels.
- a silicon microchip can be etched to form a v-groove with reflective surfaces/walls of the channels.
- optical measurements can exploit reflected, rather than transmitted, incident light. Detection can be achieved by reflection, that is by detecting reflected light. Small angle scattered light (scattered off the surfaces of any particles in the channel) is also reflected by the v-groove wall and can be collected by a small angle photodetector. Large angle scattered light and fluorescent light can exit the channel without reflection and can be collected by the a large angle photodetector.
- the reflective wall of the v-groove behind the illuminated particle enhances the fluorescence collection efficiency.
- any part of the incident light, e.g., laser beam, that is not within the v-groove channel is reflected from the silicon surface in a direction away from either the small or large angle detectors.
- the fraction of light reflected from the lid, e.g., transparent cover plate, in a case wherein light enters from air without being directly coupled into the lid/cover plate, is also directed away from the small and large angle detectors thereby reducing undesirable background light intensity from the measurements.
- microchannel system of this invention is extremely simple.
- the microchannel is fabricated from a single microchip of silicon which is patterned on a single side.
- a transparent cover plate is attached to the top of the microchip to seal the channel.
- FIG. 4 shows a v-groove flow channel and optional optical head.
- Silicon microchip 210 has v-groove 211 therein.
- the term v-groove is used herein for a substantially "V" shaped groove in the surface of a silicon microchip.
- the point of the "V” can be flat (a trapezoidal groove), but only if the flat portion does not fall within the analyte detection area defined by the interception of the illumination beam with the sample flow.
- microchip 210 has a ⁇ 100> surface orientation and the walls of groove 211 are along ⁇ 111> planes, providing an angle of 54.7° between the walls of the groove and the plane of the surface of the microchip.
- Transparent cover plate 220 is sealed to the surface of microchip 210.
- the cover plate is made of pyrex and is anodically bonded to the silicon microchip.
- the light source includes diode laser 310, optical fiber 312 and focusing head 314.
- Non-scattered light i.e., light which has not been scattered by a particle, is specularly reflected by a wall of channel 211 and travels along path 322.
- Small angle (forward) scattered light deviates slightly from path 322 and impinges on small angle detector 320. Some of the light scattered at large angles travels along path 332 to large angle photodetector 330.
- the photodetectors can be photodiodes or photomultipliers. Large angle detector 330 can be used to measure large angle scattering and/or fluorescence.
- Means for applying pressure to the flow of the feed fluids through the device can also be provided. Such means can be provided at the feed inlets and/or the outlet (e.g. as vacuum exerted by chemical or mechanical means). Means for applying such pressure are known to the art, for example as described in Shoji, S. and Esashi, M. (1994), "Microflow devices and systems," J. Micromechanics and Microengineering, 4:157-171, and include the use of a column of water or other means of applying water pressure, electroendoosmotic forces, optical forces, gravitational forces, and surface tension forces. Pressures from about 10 -6 psi to about 10 psi may be used, depending on the requirements of the system. Preferably about 10 -3 psi is used. Most preferred pressures are between about 2 mm and about 100 mm of water pressure.
- An example of an embodiment using multiple streams is a channel cell having three inlet streams flowing in laminar flow wherein the middle stream is a reagent stream.
- the sample stream may be blood, the middle stream glucose oxidase, and the third stream an indicator stream containing pH sensitive dye.
- glucose particles diffuse through the reagent stream they are changed to gluconic acid which is detected by a pH-sensitive dye when the gluconic acid molecules diffuse into the indicator stream.
- Other examples of multiple-stream systems include systems having several sample streams with analyte at different concentrations for calibration of the detection means. Indicator streams not adjacent to the sample streams may also be used as control streams.
- the indicator stream can be measured by the detection means before and after diffusion of particles into the stream has taken place, and such measurements as well as the rate of change of the indicator stream along its length can be used to assay analyte concentration.
- multiple detection means of different types can be used to measure the indicator stream. Field effects which are ion or chemical sensitive can be measured at different locations in the device.
- the channel cells of this invention and the channels therein can be sized as determined by the size of the particles desired to be detected.
- the diffusion coefficient for the analyte particles is generally inversely related to the size of the particle.
- Fluid dynamic behavior is directly related to the Reynolds number of the flow.
- the Reynolds number is the ratio of inertial forces to viscous forces. As the Reynolds number is reduced, flow patterns depend more on viscous effects and less on inertial effects. Below a certain Reynolds number, e.g., 0.1, inertial effects can essentially be ignored.
- the microfluidic devices of this invention do not require inertial effects to perform their tasks, and therefore have no inherent limit on their miniaturization due to Reynolds number effects.
- the devices of this invention require laminar, non-turbulent flow and are designed according to the foregoing principles to produce flow having low Reynolds numbers, i.e. Reynolds numbers below about 1.
- the Reynolds number is the ratio of inertial forces to viscous forces. As the Reynolds number is reduced, flow patterns depend more on viscous effects and less on inertial effects. Below a certain Reynolds number, e.g. below about 1, (based on lumen size for a system of channels with bends and lumen size changes), inertial effects can essentially be ignored.
- the microfluidic devices of this invention do not require inertial effects to perform their tasks, and therefore have no inherent limit on their miniaturization due to Reynolds number effects. Applicants' channel cell designs, while significantly different from previous reported designs, operate in this range. These microfluidic devices of this invention require laminar, non-turbulent flow and are designed according to the foregoing principles to produce flows having low Reynolds numbers.
- the devices of the preferred embodiment of this invention are capable of analyzing a sample of a size between about 0.01 microliters and about 20 microliters within a few seconds, e.g. within about three seconds. They also may be reused. Clogging is minimized and reversible.
- the sizes and velocities of 100 ⁇ m wide and 100 ⁇ m/s, for example, indicate a Reynolds number (R 3 plv/ ⁇ ) of about 10 -2 so that the fluid is in a regime where viscosity dominates over inertia.
- P eff P 0 +P st , equal to the sum of the applied pressure, P 0 , and a pressure due to the surface tension, ##EQU2##
- P st is a function of the surface tension of the fluid, ⁇ , the contact angle of the fluid with the surface, ⁇ , and the radius of curvature of the fluid surface, r.
- the size of the particles remaining in the sample stream and diffusing into the indicator stream can be controlled.
- a straight channel cell system (T-sensor) channel preferably 5-50 mm in length
- T-sensor a straight channel cell system
- silicon microchips are 3 inches, 4 inches, 6 inches, or 8 inches in diameter.
- a straight channel etched into a microchip of such size can be no longer than the microchip diameter.
- Detection of analytes with relatively small diffusion coefficients e.g. relatively large analytes or non-spherical analytes, preferably employs a convoluted flow channel.
- a convoluted flow channel as used herein refers to a flow channel which is not straight.
- FIGS. 5 and 6 show two different channel geometries which allow for longer flow channels on a typical 3-4 inch silicon microchip.
- the left and right streams e.g., sample and indicator streams
- the left and right streams have the same overall pathlength. If multiple measurements are taken in this embodiment, they should be taken along the vertical center line of the sensor so that both streams are flowing at the same flow speed and have had the same flow distance.
- the convoluted flow channel has a square wave shape like that in FIG. 5
- the streams flow at different speeds through the curves. Therefore, it may be preferable to use slower flow speeds than the speeds used in straight flow channels because the tight/narrow curves and sheer forces between the streams flowing at different speeds can cause zones in which laminar recirculation occurs. Laminar recirculation is not turbulence; the flow is still laminar and predictable. Nonetheless, laminar recirculation is not preferable and can be avoided by maintaining a Reynolds number below about 1.
- the channel cell system (T-sensor) of FIG. 6 shows a coiled/spiral flow channel.
- T-sensor The channel cell system (T-sensor) of FIG. 6 shows a coiled/spiral flow channel.
- four separate T-sensors each having a 220 mm long flow channel, can be fabricated on a single 3 inch microchip. Because the bending radius is larger in this geometry than in the square wave geometry, laminar recirculation is less likely to occur. The difference in relative flow speeds of the left and right streams (sample and indicator streams) is minimal, leading to less sheer stress between the two streams if the two streams have different viscosities.
- This channel geometry does, however, create different overall flow distances for the left and right streams.
- FIGS. 7A and 7B illustrate channel cell systems (T-sensor devices) of this invention wherein the T-joint 58 is rounded.
- FIG. 7A shows a T-sensor similar to the one shown in FIG. 1, except that the T-joint 58 is rounded in FIG. 7A.
- FIG. 7B shows a viewport T-sensor similar to the one shown in FIG. 3, except that the T-joint 58 is rounded in FIG. 7B.
- a rounded T-joint is preferable because it helps prevent laminar recirculation in the T-joint which can occur at Reynolds number above about 1.
- a rounded T-joint is preferable also because it decreases the chance of contamination of the sample stream with the indicator stream, and vice versa.
- the channel cell system of this invention can be used to measure concentration of an analyte as a function of distance (from the T-joint) rather than time.
- An increment of distance is proportional to an increment of time. With laminar flow and a known flow speed, an increment of distance can be converted to an increment of time.
- concentration or some physical property resulting from concentration, e. g., absorbance or fluorescence, versus time.
- concentration or some physical property resulting from concentration, e. g., absorbance or fluorescence
- the rate of, or rate constant for, a reaction can be determined using the T-sensor device of this invention. Detection, e.g., absorption or fluorescence measurements, can be performed at one or more analyte detection area. Referring to FIG. 8, a plurality of analyte detectors 410 can be positioned at various distances from the T-joint 58. Alternatively, one detector can be used to monitor the flow channel at various distances from the T-joint 58. FIG. 8 shows a square-wave/serpentine shaped flow channel. However, a T-sensor of any geometry which maintains laminar flow can be employed to make kinetic measurements, particularly according to the methods disclosed herein.
- a sample stream is introduced via sample stream inlet port 30 and an indicator stream is introduced via indicator stream inlet port 20.
- the two streams meet at T-joint 58.
- Analytes from the sample stream begin to diffuse into the indicator stream, and a measurable change, e.g., increase in fluorescence, occurs.
- a measurable change occurs as a result of analytes diffusing into the indicator stream, shown at analyte detection areas 90.
- the intensity of fluorescence or absorbance in the analyte detection area and the width of the analyte detection area are measured at various distances from the T-joint 58.
- the intensity and width of the analyte detection area are a function of the concentration of the analyte being measured.
- a change in color i.e. change in optical absorbance
- fluorescence occurs in the analyte detection area. This optical change becomes more intense with increasing distance from the T-joint, because the analyte and the indicator have had a longer time to interact with each other.
- the width of the analyte detection area also increases with increasing distance from the T-joint.
- the analyte detection area 90 becomes wider and more intense with increasing distance from the T-joint 58.
- a rate constant for a reaction can be determined with as few as one measurement, e.g., fluorescence at a certain distance from the T-joint.
- fluorescence e.g., fluorescence at a certain distance from the T-joint.
- increasing the number of measurements leads to increased accuracy of the kinetic rate constant calculated from such measurements.
- the T-sensor channel cell system of this invention can comprise branching flow channels 401 and 402 as illustrated in FIG. 9A.
- the sample containing small molecules of interest is brought into the device through sample stream inlet port 30, from whence it flows into sample stream inlet channel 50.
- An indicator stream is brought into indicator stream inlet port 20, from whence it flows into indicator stream inlet channel 40.
- the two streams flow parallel to one another in laminar flow, and small molecules (analytes) from the sample stream diffuse into the indicator stream.
- Branching flow channels as used herein refer to flow channels in fluid connection with the flow channel 100.
- a W-joint 400 as shown in FIGS. 9A and 9B may be used to correct the branching flow channels 401 and 402 with flow channel 100.
- Branching flow channels allow for detection of both undissolved and dissolved particles.
- a detector preferably positioned above or below the device, monitors the flow channel 100 and v-grooves 403 or 404.
- This dual detection embodiment can detect dissolved and undissolved particles in the flow channel 100 as well as undissolved particles flowing in single file fashion in the v-groove(s).
- Particle detection can be performed by standard optical techniques, e.g., imaging, light scattering, or spectroscopy, as the particles flow through one or both of the v-grooves 403 or 404, which are in fluid connection with branching flow channels 401 and 402, respectively.
- Branching flow channels 401 and 402 are in fluid connection with exit ports 405 and 406, respectively.
- a sample e.g., whole blood
- a buffered solution containing reporter beads can be introduced via indicator stream inlet port 20 from when it flows into indicator stream inlet channel 40.
- the sample and indicator stream flow parallel to each other in laminar flow in flow channel 100. Small analytes in the sample, e.g., protons, diffuse into the indicator stream.
- the sample flows into branching flow channel 402 and then into v-groove 404, through which particles, e.g., red and white blood cells, flow in single file fashion.
- the reporter beads flow into branching flow channel 402 and then into v-groove 403, through which the beads flow in single file fashion.
- An optical detector preferably positioned above or below the device simultaneously monitors the two streams in flow channel 100 and the undissolved sample particles in v-groove 404 and beads in v-groove 403, the beads being indicators of dissolved sample analytes.
- the indicator stream can include a dissolved indicator dye which is monitored with the monitoring of the undissolved sample particles when this embodiment of the present device is employed.
- a dissolved indicator dye does not need to be monitored in a v-groove.
- both branching flow channels need not be connected to v-grooves, as illustrated in FIG. 9C.
- a sample of whole blood can be monitored in a v-groove channel to detect the number of white blood cells. Then the same sample flows into a T-sensor in fluid connection with the v-groove channel. In the T-sensor the white blood cells react with fluorescent reporter beads tagged with an antibody. Then the sample flows into another v-groove channel in fluid connection with the T-sensor. In this v-groove channel the white blood cells are identified by fluorescence.
- the T-sensor channel system of the present invention can further comprise a waste port 407, as illustrated in FIG. 9B.
- a waste port 407 to insure that only sample stream enters branching flow channel 402, and that only indicator stream enters branching flow channel 401, a portion of each stream can be diverted to a waste port 407.
- the waste port is in fluid connection with the flow channels at the W-joint to divert a portion of each stream to a waste outlet.
- FIG. 9C illustrates sample stream (represented by x) and indicator stream (represented by squares) flowing through the channel system of this invention comprising branching flow channels and a waste port.
- FIG. 9C further illustrates that the branching flow channels do not have to loop back and run parallel to the flow channel 100.
- Branching flow channels can connect to the flow channel 100 in any angle desired. In order to monitor the flow through the various channels simultaneously and with one detector it is preferable that the branching flow channels connect with the flow channel 100 at an angle which allows for such monitoring.
- Detection of dissolved and undissolved particles in one device employing this embodiment is economically advantageous, as measurements can be performed with only one set of pumps and one detector.
- a sample can first flow through a flow channel of a T-sensor where the sample reacts with reporter beads, e.g., an analyte in the sample diffuses into an indicator stream containing reporter beads.
- reporter beads e.g., an analyte in the sample diffuses into an indicator stream containing reporter beads.
- the fluid containing reporter beads can then flow into a sheath flow module in fluid connection with the T-sensor flow channel.
- the beads are focused so that they flow in single file fashion for detection.
- FIG. 10A is a lengthwise section through the center of a flow module, as described in U.S. Patent Application "Device and Method for 3-Dimensional Alignment of Particles in Microfabricated Flow Channels," (filed Mar. 26, 1997).
- Plate 501 is machined, molded or etched to form the flow channel.
- the plate can be selected from the following which include, but are not limited to, silicon wafers, plastics, e.g., polypropylene, and casting materials.
- a laminar flow channel 508 is formed in a flat plane of the plate.
- a first inlet 510 passes through the plate at the upstream end of the channel and joins the flow channel at first inlet junction 511.
- An outlet 530 passes through the plate at the downstream end of the channel and joins the flow channel at outlet junction 531.
- a second inlet 520 passes through the plate between the first inlet and the outlet and joins the flow channel at second inlet junction 521, which is narrower than the first inlet junction.
- a second plate 505 is sealed to the flat plane of the first plate, thereby forming one side of the laminar flow channel. A view of the channel surface is illustrated in FIG. 10B.
- FIG. 10C is a cross section of the flow channel of FIGS. 10A and 10B, illustrating the sheath flow attained in one embodiment of the present invention.
- flow channel 508 is trapezoidal.
- a center fluid 554, injected from inlet 520, is surrounded on both sides (left and right) and on top by a sheath fluid 553.
- a T-sensor channel system can be etched all the way through a substrate plate, e.g., a silicon microchip or other slab of material. The entire channel system can be etched all the way through, and therefore transect, that is, extend through the width of, the substrate plate. Alternatively, only that part of the channel system comprising the analyte detection area 90 can be etched all the way through, and therefore extend through the width of, the substrate plate, as shown in FIG. 11. Indicator stream inlet port 20, sample stream inlet port 30, and exit port 60 are shown also.
- An optically transparent plate e.g., a cover plate, is sealed to both sides of the microchip. If only part of the channel system is etched all the way through the microchip, then the transparent plate need cover only that part of the microchip.
- the dimensions of the device are chosen so that laminar flow is maintained.
- a silicon microchip is etched by anisotropic EPW etching, it is preferable to use a thin microchip so that the channel diameters can be kept small enough to maintain laminar flow.
- the anisotropic EPW etching creates channels which are wider at the top than at the bottom of the channel. Etching all the way through a microchip can create a channel which is undesirably wide at the top and therefore with an undesirably large channel diameter. Undesirably large channel diameters may not maintain laminar flow.
- Preferable widths of a thin microchip are between 100 and 300 microns, and more preferably between 100 and 200 microns.
- etching silicon e.g., reactive ion etching
- a microchip can be made thinner by etching prior to formation of the channel system therein.
- An uncoated microchip that is a microchip with no photoresist on it, can be made thinner by submerging it in etching solution.
- a channel system, or at least the analyte detection area, can then be etched all the way through the microchip.
- a T-sensor channel system which maintains a low Reynolds number, i.e. laminar flow, can be formed wherein the depth of the channel is greater than the width.
- the channel dimensions are such that diffusion from top to bottom and bottom to top counteracts this parabolic flow speed profile. Increasing the depth of the flow channel decreases the effect of diffusion from top to bottom and bottom to top.
- a two-mask level process was used to fabricate a channel cell of this invention on a silicon wafer.
- the channel cell had a flow channel 400 micrometers wide and 20 mm long.
- the "branches" or crossbar of the "T” comprising the inlet channels was a groove 30 mm long and 200 micrometers wide.
- Channel depth was 50 micrometers.
- the first mask level defined the inlets and outlet ports, which were etched completely through the wafer to the rear side of the silicon.
- the second level defined the fluid transport channels.
- Wafers were cleaned in a Piranha bath (H 2 SO 4 and H 2 O 2 ) (2:1) before processing.
- a primer (HMDS spun on at 3000 rpm) was used to enhance photoresist adhesion.
- About one ⁇ m of AZ-1370-SF (Hoechst) photoresist was deposited by spin coating (3000 rpm), and this was followed by a soft bake (30 min at 90° C.).
- a contact aligner was used to align and expose wafers. Exposure time was varied to yield best results. No post-exposure bake was done. Wafers were developed in AZ-351 (diluted 4: 1) (Hoechst) for one minute and rinsed in DI water. Blue tack tape (Semiconductor Equipment Corporation, Moorpark, Calif.) was applied to the backsides of the wafers to protect the oxide from the oxide etch.
- the wafers were immersed in a buffered oxide etch (BOE, 10:1 HF (49%) and NH 4 F (10%)) for eleven minutes to completely etch away the unprotected oxide.
- BOE buffered oxide etch
- the blue tack tape was removed by hand, and the photoresist was removed in an acetone rinse.
- Silicon etching was done in a mixture of ethylene-diamine, pyro-catechol, and water (EPW F-etch as described in Reisman, A., et al. (1979) J. Electrochem. Soc. 126:1406-1415) set up in a reflux boiling flask. This etch attacks the ⁇ 100 ⁇ planes of silicon at a rate of about 100 ⁇ m an hour. Fluid attachment ports were etched in the first step for about three hours. Photoresist was again applied, and the mask containing flow channels between fluid ports and the barrier region was exposed. The wafers were developed and etched in this second step for about one hour.
- the wafers were once again cleaned in a Piranha bath and rinsed in DI water. They were then diced into individual devices about 1 cm by 1 cm.
- the T-sensor channel cell was attached to the stage of a microscope so that the joint of the T-sensor was in the view field of the objective.
- the inlet ports and the outlet port were connected to injector loops and to upright tubes which were filled with water so that there was a pressure difference of 30 mm water column between the inlet ports and the outlet port. Both inlet ports were exposed to identical pressure so that the two streams joined in the middle of the T-joint, and were flowing parallel to the outlet port.
- One injector loop was filed with indicator dye solution, the other loop was filled with one of the sample solutions. The loops contained enough volume to operate the device for roughly one hour.
- the excitation filter center wavelength was 480 nm
- the emission filter was a longpass 510 nm filter.
- the experiment yielded photographs in which the color of the analyte detection area between the indicator stream and the sample stream was a function of the pH of the sample stream.
- the color changed from red over orange to yellow as the pH decreased from 8.0 to 7.2.
- Computer-enhanced images showed the color of the indicator stream per se to be yellow, and the analyte detection area between the streams to range from red to orange, whereas the colorless ample stream appeared black.
- color mapping numeric values are assigned to the different colors which are used to calibrate the system.
- light intensity change is measured at two wavelengths, thereby measuring the decrease of the red portion and the increase of the yellow portion of the spectrum with decreasing pH.
- the alkaline phosphatase catalyzed the reaction of PNPP to p-nitrophenol (strongly yellow) and phosphate.
- the formation, (and rate thereof), of p-nitrophenol was detected by an increase in yellow color.
- the rate of change of yellow color intensity as a function of distance from the T-joint was a function of enzyme concentration, enabling calculation of a rate constant.
Abstract
Description
Claims (19)
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/829,679 US5972710A (en) | 1996-03-29 | 1997-03-31 | Microfabricated diffusion-based chemical sensor |
US08/900,926 US5948684A (en) | 1997-03-31 | 1997-07-25 | Simultaneous analyte determination and reference balancing in reference T-sensor devices |
US09/366,821 US6171865B1 (en) | 1996-03-29 | 1999-08-04 | Simultaneous analyte determination and reference balancing in reference T-sensor devices |
US09/574,797 US6541213B1 (en) | 1996-03-29 | 2000-05-19 | Microscale diffusion immunoassay |
US09/702,645 US6582963B1 (en) | 1996-03-29 | 2000-10-31 | Simultaneous analyte determination and reference balancing in reference T-sensor devices |
US09/703,764 US6454945B1 (en) | 1995-06-16 | 2000-11-01 | Microfabricated devices and methods |
US10/277,047 US20030211507A1 (en) | 1996-03-29 | 2002-10-21 | Microscale diffusion immunoassay in hydrogels |
US10/368,511 US7271007B2 (en) | 1996-03-29 | 2003-02-18 | Microscale diffusion immunoassay |
US11/054,711 US20060073599A1 (en) | 1995-06-16 | 2005-02-08 | Microfabricated diffusion-based chemical sensor |
US11/165,619 US20060115905A1 (en) | 1996-03-29 | 2005-06-23 | Microscale diffusion immunoassay in hydrogels |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/625,808 US5716852A (en) | 1996-03-29 | 1996-03-29 | Microfabricated diffusion-based chemical sensor |
US08/829,679 US5972710A (en) | 1996-03-29 | 1997-03-31 | Microfabricated diffusion-based chemical sensor |
Related Parent Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US08/625,808 Continuation-In-Part US5716852A (en) | 1995-06-16 | 1996-03-29 | Microfabricated diffusion-based chemical sensor |
US08/625,808 Continuation US5716852A (en) | 1995-06-16 | 1996-03-29 | Microfabricated diffusion-based chemical sensor |
Related Child Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US08/625,808 Continuation-In-Part US5716852A (en) | 1995-06-16 | 1996-03-29 | Microfabricated diffusion-based chemical sensor |
US08/663,916 Continuation-In-Part US5932100A (en) | 1995-06-16 | 1996-06-14 | Microfabricated differential extraction device and method |
US08/900,926 Continuation-In-Part US5948684A (en) | 1996-03-29 | 1997-07-25 | Simultaneous analyte determination and reference balancing in reference T-sensor devices |
US42668399A Continuation | 1995-06-16 | 1999-10-25 | |
US10/277,047 Continuation US20030211507A1 (en) | 1996-03-29 | 2002-10-21 | Microscale diffusion immunoassay in hydrogels |
Publications (1)
Publication Number | Publication Date |
---|---|
US5972710A true US5972710A (en) | 1999-10-26 |
Family
ID=24507689
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US08/625,808 Expired - Lifetime US5716852A (en) | 1995-06-16 | 1996-03-29 | Microfabricated diffusion-based chemical sensor |
US08/829,679 Expired - Lifetime US5972710A (en) | 1995-06-16 | 1997-03-31 | Microfabricated diffusion-based chemical sensor |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US08/625,808 Expired - Lifetime US5716852A (en) | 1995-06-16 | 1996-03-29 | Microfabricated diffusion-based chemical sensor |
Country Status (6)
Country | Link |
---|---|
US (2) | US5716852A (en) |
EP (1) | EP0890094B1 (en) |
JP (2) | JP2001504936A (en) |
AU (1) | AU3877797A (en) |
DE (1) | DE69724943T2 (en) |
WO (1) | WO1997039338A1 (en) |
Cited By (215)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6134950A (en) * | 1997-06-13 | 2000-10-24 | University Of Washington | Method for determining concentration of a laminar sample stream |
WO2000070080A1 (en) * | 1999-05-17 | 2000-11-23 | Caliper Technologies Corp. | Focusing of microparticles in microfluidic systems |
WO2000072020A1 (en) * | 1999-05-21 | 2000-11-30 | University Of Washington | Microscale diffusion immunoassay |
US6159739A (en) * | 1997-03-26 | 2000-12-12 | University Of Washington | Device and method for 3-dimensional alignment of particles in microfabricated flow channels |
US6171865B1 (en) * | 1996-03-29 | 2001-01-09 | University Of Washington | Simultaneous analyte determination and reference balancing in reference T-sensor devices |
US6210986B1 (en) * | 1999-09-23 | 2001-04-03 | Sandia Corporation | Microfluidic channel fabrication method |
US6221677B1 (en) * | 1997-09-26 | 2001-04-24 | University Of Washington | Simultaneous particle separation and chemical reaction |
US6277641B1 (en) * | 1997-09-26 | 2001-08-21 | University Of Washington | Methods for analyzing the presence and concentration of multiple analytes using a diffusion-based chemical sensor |
US20010042712A1 (en) * | 2000-05-24 | 2001-11-22 | Battrell C. Frederick | Microfluidic concentration gradient loop |
WO2002023161A1 (en) * | 2000-09-18 | 2002-03-21 | University Of Washington | Microfluidic devices for rotational manipulation of the fluidic interface between multiple flow streams |
US6368871B1 (en) * | 1997-08-13 | 2002-04-09 | Cepheid | Non-planar microstructures for manipulation of fluid samples |
US20020045246A1 (en) * | 1999-06-25 | 2002-04-18 | Cepheid | Device for lysing cells, spores, or microorganisms |
US6382228B1 (en) | 2000-08-02 | 2002-05-07 | Honeywell International Inc. | Fluid driving system for flow cytometry |
US6404493B1 (en) | 1998-10-09 | 2002-06-11 | University Of Washington | Dual large angle light scattering detection |
US6408884B1 (en) | 1999-12-15 | 2002-06-25 | University Of Washington | Magnetically actuated fluid handling devices for microfluidic applications |
US6431476B1 (en) | 1999-12-21 | 2002-08-13 | Cepheid | Apparatus and method for rapid ultrasonic disruption of cells or viruses |
US6440725B1 (en) | 1997-12-24 | 2002-08-27 | Cepheid | Integrated fluid manipulation cartridge |
US20020127740A1 (en) * | 2001-03-06 | 2002-09-12 | Ho Winston Z. | Quantitative microfluidic biochip and method of use |
WO2002077259A2 (en) * | 2001-03-24 | 2002-10-03 | Aviva Biosciences Corporation | Biochips including ion transport detecting structures and methods of use |
US6488896B2 (en) * | 2000-03-14 | 2002-12-03 | Micronics, Inc. | Microfluidic analysis cartridge |
WO2003020886A2 (en) * | 2001-08-29 | 2003-03-13 | Celtor Biosystems | Methods and devices for detecting cell-cell interactions |
US20030058445A1 (en) * | 2000-08-02 | 2003-03-27 | Fritz Bernard S. | Optical alignment detection system |
US6541213B1 (en) * | 1996-03-29 | 2003-04-01 | University Of Washington | Microscale diffusion immunoassay |
US6549275B1 (en) | 2000-08-02 | 2003-04-15 | Honeywell International Inc. | Optical detection system for flow cytometry |
US6576194B1 (en) * | 1998-05-18 | 2003-06-10 | University Of Washington | Sheath flow assembly |
US20030124623A1 (en) * | 2001-12-05 | 2003-07-03 | Paul Yager | Microfluidic device and surface decoration process for solid phase affinity binding assays |
US6592821B1 (en) * | 1999-05-17 | 2003-07-15 | Caliper Technologies Corp. | Focusing of microparticles in microfluidic systems |
US6597438B1 (en) | 2000-08-02 | 2003-07-22 | Honeywell International Inc. | Portable flow cytometry |
US20030142291A1 (en) * | 2000-08-02 | 2003-07-31 | Aravind Padmanabhan | Portable scattering and fluorescence cytometer |
US20030157586A1 (en) * | 2002-02-21 | 2003-08-21 | Martin Bonde | Device and method for conducting cellular assays using multiple fluid flow |
US6613580B1 (en) * | 1999-07-06 | 2003-09-02 | Caliper Technologies Corp. | Microfluidic systems and methods for determining modulator kinetics |
EP1339496A2 (en) * | 2000-11-06 | 2003-09-03 | The Government of the United States of America, as represented by the Secretary of Health and Human Services | Sample delivery system with laminar mixing for microvolume biosensing |
US20030175944A1 (en) * | 2002-03-18 | 2003-09-18 | Mengsu Yang | Apparatus and methods for on-chip monitoring of cellular reactions |
US20030203504A1 (en) * | 2002-04-26 | 2003-10-30 | John Hefti | Diffusion-based system and method for detecting and monitoring activity of biologic and chemical species |
US20040004716A1 (en) * | 2002-07-05 | 2004-01-08 | Rashid Mavliev | Method and apparatus for detecting individual particles in a flowable sample |
US20040028559A1 (en) * | 2001-11-06 | 2004-02-12 | Peter Schuck | Sample delivery system with laminar mixing for microvolume biosensing |
US6700130B2 (en) | 2001-06-29 | 2004-03-02 | Honeywell International Inc. | Optical detection system for flow cytometry |
US20040063151A1 (en) * | 2002-04-24 | 2004-04-01 | Beebe David J. | Method of performing gradient-based assays in a microfluidic device |
US6743399B1 (en) * | 1999-10-08 | 2004-06-01 | Micronics, Inc. | Pumpless microfluidics |
US20040145725A1 (en) * | 2001-06-29 | 2004-07-29 | Fritz Bernard S. | Optical detection system for flow cytometry |
US20040146849A1 (en) * | 2002-01-24 | 2004-07-29 | Mingxian Huang | Biochips including ion transport detecting structures and methods of use |
US20040168982A1 (en) * | 2003-03-01 | 2004-09-02 | Hemanext, L.L.C. | Microvascular network device |
US20040200909A1 (en) * | 1999-05-28 | 2004-10-14 | Cepheid | Apparatus and method for cell disruption |
US20040211077A1 (en) * | 2002-08-21 | 2004-10-28 | Honeywell International Inc. | Method and apparatus for receiving a removable media member |
US6825127B2 (en) | 2001-07-24 | 2004-11-30 | Zarlink Semiconductor Inc. | Micro-fluidic devices |
US6830729B1 (en) | 1998-05-18 | 2004-12-14 | University Of Washington | Sample analysis instrument |
US20040256230A1 (en) * | 1999-06-03 | 2004-12-23 | University Of Washington | Microfluidic devices for transverse electrophoresis and isoelectric focusing |
US20040266022A1 (en) * | 2003-06-26 | 2004-12-30 | Narayanan Sundararajan | Hydrodynamic Focusing Devices |
US20040265183A1 (en) * | 2003-06-26 | 2004-12-30 | Narayanan Sundararajan | Fabricating structures in micro-fluidic channels based on hydrodynamic focusing |
US20050009004A1 (en) * | 2002-05-04 | 2005-01-13 | Jia Xu | Apparatus including ion transport detecting structures and methods of use |
US20050009101A1 (en) * | 2001-05-17 | 2005-01-13 | Motorola, Inc. | Microfluidic devices comprising biochannels |
US6843963B1 (en) * | 1998-05-25 | 2005-01-18 | Herbert Peter Jennissen | Flow-through shear analyzer for biologically active molecules in liquid layers on surfaces |
US6858185B1 (en) * | 1999-08-25 | 2005-02-22 | Caliper Life Sciences, Inc. | Dilutions in high throughput systems with a single vacuum source |
US20050058990A1 (en) * | 2001-03-24 | 2005-03-17 | Antonio Guia | Biochip devices for ion transport measurement, methods of manufacture, and methods of use |
US20050072967A1 (en) * | 2003-10-07 | 2005-04-07 | Pavel Kornilovich | Fabrication of nanowires |
US20050078299A1 (en) * | 2000-08-02 | 2005-04-14 | Fritz Bernard S. | Dual use detectors for flow cytometry |
US20050105077A1 (en) * | 2000-08-02 | 2005-05-19 | Aravind Padmanabhan | Miniaturized cytometer for detecting multiple species in a sample |
US20050118723A1 (en) * | 2000-08-02 | 2005-06-02 | Aravind Padmanabhan | Optical detection system with polarizing beamsplitter |
US20050129582A1 (en) * | 2003-06-06 | 2005-06-16 | Micronics, Inc. | System and method for heating, cooling and heat cycling on microfluidic device |
US20050134850A1 (en) * | 2000-08-02 | 2005-06-23 | Tom Rezachek | Optical alignment system for flow cytometry |
WO2005057186A1 (en) * | 2003-12-10 | 2005-06-23 | Biacore Ab | Sample flow positioning method and analytical system using the method |
US6936496B2 (en) | 2002-12-20 | 2005-08-30 | Hewlett-Packard Development Company, L.P. | Nanowire filament |
US20050196746A1 (en) * | 2001-03-24 | 2005-09-08 | Jia Xu | High-density ion transport measurement biochip devices and methods |
US20050199076A1 (en) * | 2003-12-10 | 2005-09-15 | Biacore Ab | Sample flow positioning method and analytical system using the method |
US20050221235A1 (en) * | 2004-04-02 | 2005-10-06 | Pavel Kornilovich | Fabrication and use of superlattice |
US20050243304A1 (en) * | 2000-08-02 | 2005-11-03 | Honeywell International Inc. | Cytometer analysis cartridge optical configuration |
US20050241959A1 (en) * | 2004-04-30 | 2005-11-03 | Kenneth Ward | Chemical-sensing devices |
US20050255472A1 (en) * | 2002-07-19 | 2005-11-17 | Kenichi Yamashita | Molecule analyzing method using microchannel |
US20050255001A1 (en) * | 2004-05-14 | 2005-11-17 | Honeywell International Inc. | Portable sample analyzer with removable cartridge |
US20050255600A1 (en) * | 2004-05-14 | 2005-11-17 | Honeywell International Inc. | Portable sample analyzer cartridge |
US20050266478A1 (en) * | 2002-01-24 | 2005-12-01 | Mingxian Huang | Biochips including ion transport detecting structures and methods of use |
US20060023207A1 (en) * | 2004-07-27 | 2006-02-02 | Cox James A | Cytometer having fluid core stream position control |
US20060024814A1 (en) * | 2004-07-29 | 2006-02-02 | Peters Kevin F | Aptamer-functionalized electrochemical sensors and methods of fabricating and using the same |
US20060029955A1 (en) * | 2001-03-24 | 2006-02-09 | Antonio Guia | High-density ion transport measurement biochip devices and methods |
US20060034685A1 (en) * | 2004-07-07 | 2006-02-16 | Nobuaki Kizuka | Gas turbine and gas turbine cooling method |
US20060046300A1 (en) * | 2004-09-02 | 2006-03-02 | Aravind Padmanabhan | Method and apparatus for determining one or more operating parameters for a microfluidic circuit |
US20060051096A1 (en) * | 2004-09-01 | 2006-03-09 | Cox James A | Frequency-multiplexed detection of multiple wavelength light for flow cytometry |
US20060066852A1 (en) * | 2004-09-27 | 2006-03-30 | Fritz Bernard S | Data frame selection for cytometer analysis |
US20060066840A1 (en) * | 2002-08-21 | 2006-03-30 | Fritz Bernard S | Cytometer having telecentric optics |
US7027683B2 (en) | 2000-08-15 | 2006-04-11 | Nanostream, Inc. | Optical devices with fluidic systems |
US20060106557A1 (en) * | 2004-11-18 | 2006-05-18 | Fontaine Norman H | System and method for self-referencing a sensor in a micron-sized deep flow chamber |
US20060108012A1 (en) * | 2002-11-14 | 2006-05-25 | Barrow David A | Microfluidic device and methods for construction and application |
US20060115905A1 (en) * | 1996-03-29 | 2006-06-01 | University Of Washington | Microscale diffusion immunoassay in hydrogels |
US7061595B2 (en) | 2000-08-02 | 2006-06-13 | Honeywell International Inc. | Miniaturized flow controller with closed loop regulation |
US20060138079A1 (en) * | 2004-12-27 | 2006-06-29 | Potyrailo Radislav A | Fabrication process of microfluidic devices |
US20060166375A1 (en) * | 2004-09-23 | 2006-07-27 | University Of Washington | Microscale diffusion immunoassay utilizing multivalent reactants |
US20060194420A1 (en) * | 2005-02-28 | 2006-08-31 | Pavel Kornilovich | Multilayer film |
US20060244964A1 (en) * | 2005-04-29 | 2006-11-02 | Honeywell International Inc. | Particle parameter determination system |
US7132298B2 (en) | 2003-10-07 | 2006-11-07 | Hewlett-Packard Development Company, L.P. | Fabrication of nano-object array |
US20060263888A1 (en) * | 2000-06-02 | 2006-11-23 | Honeywell International Inc. | Differential white blood count on a disposable card |
US20060263256A1 (en) * | 2005-05-17 | 2006-11-23 | Nitrex Metal Inc. | Apparatus and method for controlling atmospheres in heat treating of metals |
US20070041013A1 (en) * | 2005-08-16 | 2007-02-22 | Honeywell International Inc. | A light scattering and imaging optical system |
US20070166195A1 (en) * | 2004-05-14 | 2007-07-19 | Honeywell International Inc. | Analyzer system |
US7247531B2 (en) | 2004-04-30 | 2007-07-24 | Hewlett-Packard Development Company, L.P. | Field-effect-transistor multiplexing/demultiplexing architectures and methods of forming the same |
US20080080306A1 (en) * | 2004-10-11 | 2008-04-03 | Technische Universitat Darmstadt | Microcapillary reactor and method for controlled mixing of nonhomogeneously miscible fluids using said microcapillary reactor |
FR2907228A1 (en) * | 2006-10-13 | 2008-04-18 | Rhodia Recherches & Tech | FLUID FLOW DEVICE, ASSEMBLY FOR DETERMINING AT LEAST ONE CHARACTERISTIC OF A PHYSICO-CHEMICAL SYSTEM COMPRISING SUCH A DEVICE, DETERMINING METHOD AND CORRESPONDING SCREENING METHOD |
US7405054B1 (en) | 2004-12-13 | 2008-07-29 | University Of Washington Uw Tech Transfer - Invention Licensing | Signal amplification method for surface plasmon resonance-based chemical detection |
US20080181821A1 (en) * | 2007-01-29 | 2008-07-31 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Microfluidic chips for allergen detection |
US20080202931A1 (en) * | 2006-06-15 | 2008-08-28 | Dimiter Nikolov Petsev | Ion Specific Control of the Transport of Fluid and Current in Fluidic Nanochannels |
EP1970346A2 (en) | 2007-03-15 | 2008-09-17 | DALSA Semiconductor Inc. | Microchannels for biomens devices |
WO2008110147A1 (en) * | 2007-03-09 | 2008-09-18 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Flow channel system and method for connecting analytes to ligands |
US20080241000A1 (en) * | 2007-03-27 | 2008-10-02 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Systems for pathogen detection |
EP1982768A2 (en) | 2007-03-27 | 2008-10-22 | Searete LLC | Methods for pathogen detection |
US20090042241A1 (en) * | 2007-04-06 | 2009-02-12 | California Institute Of Technology | Microfluidic device |
US20090053814A1 (en) * | 2005-08-11 | 2009-02-26 | Eksigent Technologies, Llc | Microfluidic apparatus and method for sample preparation and analysis |
US20090068760A1 (en) * | 2007-09-11 | 2009-03-12 | University Of Washington | Microfluidic assay system with dispersion monitoring |
US20090081771A1 (en) * | 2003-06-06 | 2009-03-26 | Micronics, Inc. | System and method for heating, cooling and heat cycling on microfluidic device |
US20090086249A1 (en) * | 2007-10-01 | 2009-04-02 | Brother Kogyo Kabushiki Kaisha | Image formation device and computer-readable record medium |
WO2007021820A3 (en) * | 2005-08-11 | 2009-04-23 | Eksigent Technologies Llc | Methods for measuring biochemical reactions |
US20090139576A1 (en) * | 2005-08-11 | 2009-06-04 | Eksigent Technologies, Llc | Microfluidic systems, devices and methods for reducing noise generated by mechanical instabilities |
US20090148847A1 (en) * | 2006-03-15 | 2009-06-11 | Micronics, Inc. | Rapid magnetic flow assays |
US7553453B2 (en) | 2000-06-02 | 2009-06-30 | Honeywell International Inc. | Assay implementation in a microfluidic format |
US20090263284A1 (en) * | 1998-01-20 | 2009-10-22 | Ge Healthcare Bio-Sciences Ab | Method and device for laminar flow on a sensing surface |
US20090268548A1 (en) * | 2005-08-11 | 2009-10-29 | Eksigent Technologies, Llc | Microfluidic systems, devices and methods for reducing diffusion and compliance effects at a fluid mixing region |
US7630075B2 (en) | 2004-09-27 | 2009-12-08 | Honeywell International Inc. | Circular polarization illumination based analyzer system |
US20090325276A1 (en) * | 2006-09-27 | 2009-12-31 | Micronics, Inc. | Integrated microfluidic assay devices and methods |
US20100007879A1 (en) * | 2008-07-08 | 2010-01-14 | Rashid Mavliev | Systems and methods for in-line monitoring of particles in opaque flows |
US20100068706A1 (en) * | 1998-12-24 | 2010-03-18 | Cepheid | Method for separating an analyte from a sample |
US7683435B2 (en) | 2004-04-30 | 2010-03-23 | Hewlett-Packard Development Company, L.P. | Misalignment-tolerant multiplexing/demultiplexing architectures |
US20100081216A1 (en) * | 2006-10-04 | 2010-04-01 | Univeristy Of Washington | Method and device for rapid parallel microfluidic molecular affinity assays |
US7713687B2 (en) | 2000-11-29 | 2010-05-11 | Xy, Inc. | System to separate frozen-thawed spermatozoa into x-chromosome bearing and y-chromosome bearing populations |
US7723116B2 (en) | 2003-05-15 | 2010-05-25 | Xy, Inc. | Apparatus, methods and processes for sorting particles and for providing sex-sorted animal sperm |
US20100167384A1 (en) * | 2005-11-30 | 2010-07-01 | Micronics, Inc, | Microfluidic mixing and analytical apparatus |
EP2204348A2 (en) | 2009-01-05 | 2010-07-07 | DALSA Semiconductor Inc. | Method of making bio MEMS devices |
US7758811B2 (en) | 2003-03-28 | 2010-07-20 | Inguran, Llc | System for analyzing particles using multiple flow cytometry units |
US7767447B2 (en) | 2007-06-21 | 2010-08-03 | Gen-Probe Incorporated | Instruments and methods for exposing a receptacle to multiple thermal zones |
US7820425B2 (en) | 1999-11-24 | 2010-10-26 | Xy, Llc | Method of cryopreserving selected sperm cells |
US7827042B2 (en) | 2005-11-30 | 2010-11-02 | The Invention Science Fund I, Inc | Methods and systems related to transmission of nutraceutical associated information |
US20100279393A1 (en) * | 2009-02-05 | 2010-11-04 | Taisuke Hirono | Micro chip device |
US7833147B2 (en) | 2004-07-22 | 2010-11-16 | Inguran, LLC. | Process for enriching a population of sperm cells |
US7838210B2 (en) | 2004-03-29 | 2010-11-23 | Inguran, LLC. | Sperm suspensions for sorting into X or Y chromosome-bearing enriched populations |
US7855078B2 (en) | 2002-08-15 | 2010-12-21 | Xy, Llc | High resolution flow cytometer |
US7929137B2 (en) | 1997-01-31 | 2011-04-19 | Xy, Llc | Optical apparatus |
US7927787B2 (en) | 2006-06-28 | 2011-04-19 | The Invention Science Fund I, Llc | Methods and systems for analysis of nutraceutical associated components |
US7974856B2 (en) | 2005-11-30 | 2011-07-05 | The Invention Science Fund I, Llc | Computational systems and methods related to nutraceuticals |
US8000981B2 (en) | 2005-11-30 | 2011-08-16 | The Invention Science Fund I, Llc | Methods and systems related to receiving nutraceutical associated information |
US8034296B2 (en) | 2005-07-01 | 2011-10-11 | Honeywell International Inc. | Microfluidic card for RBC analysis |
US8068991B2 (en) | 2005-11-30 | 2011-11-29 | The Invention Science Fund I, Llc | Systems and methods for transmitting pathogen related information and responding |
US8137967B2 (en) | 2000-11-29 | 2012-03-20 | Xy, Llc | In-vitro fertilization systems with spermatozoa separated into X-chromosome and Y-chromosome bearing populations |
US8211629B2 (en) | 2002-08-01 | 2012-07-03 | Xy, Llc | Low pressure sperm cell separation system |
EP2490005A1 (en) * | 2011-02-18 | 2012-08-22 | Koninklijke Philips Electronics N.V. | Microfluidic resistance network and microfluidic device |
US8273294B2 (en) | 2005-07-01 | 2012-09-25 | Honeywell International Inc. | Molded cartridge with 3-D hydrodynamic focusing |
US8297028B2 (en) | 2006-06-14 | 2012-10-30 | The Invention Science Fund I, Llc | Individualized pharmaceutical selection and packaging |
US8323564B2 (en) | 2004-05-14 | 2012-12-04 | Honeywell International Inc. | Portable sample analyzer system |
US8340944B2 (en) | 2005-11-30 | 2012-12-25 | The Invention Science Fund I, Llc | Computational and/or control systems and methods related to nutraceutical agent selection and dosing |
US20130011928A1 (en) * | 2010-03-29 | 2013-01-10 | Analogic Corporation | Optical detection system and/or method |
US8359484B2 (en) | 2008-09-18 | 2013-01-22 | Honeywell International Inc. | Apparatus and method for operating a computing platform without a battery pack |
US8361410B2 (en) | 2005-07-01 | 2013-01-29 | Honeywell International Inc. | Flow metered analyzer |
US8486618B2 (en) | 2002-08-01 | 2013-07-16 | Xy, Llc | Heterogeneous inseminate system |
US8535421B2 (en) | 2009-10-12 | 2013-09-17 | New Health Sciences, Inc. | Blood storage bag system and depletion devices with oxygen and carbon dioxide depletion capabilities |
US8569052B2 (en) | 2009-10-12 | 2013-10-29 | New Health Sciences, Inc. | Oxygen depletion devices and methods for removing oxygen from red blood cells |
US8617903B2 (en) | 2007-01-29 | 2013-12-31 | The Invention Science Fund I, Llc | Methods for allergen detection |
US8663583B2 (en) | 2011-12-27 | 2014-03-04 | Honeywell International Inc. | Disposable cartridge for fluid analysis |
US8741233B2 (en) | 2011-12-27 | 2014-06-03 | Honeywell International Inc. | Disposable cartridge for fluid analysis |
US8741235B2 (en) | 2011-12-27 | 2014-06-03 | Honeywell International Inc. | Two step sample loading of a fluid analysis cartridge |
US8741234B2 (en) | 2011-12-27 | 2014-06-03 | Honeywell International Inc. | Disposable cartridge for fluid analysis |
US8784012B2 (en) * | 2007-04-16 | 2014-07-22 | The General Hospital Corporation | Systems and methods for particle focusing in microchannels |
US8815521B2 (en) | 2000-05-30 | 2014-08-26 | Cepheid | Apparatus and method for cell disruption |
US8828320B2 (en) | 2004-05-14 | 2014-09-09 | Honeywell International Inc. | Portable sample analyzer cartridge |
US8828226B2 (en) | 2003-03-01 | 2014-09-09 | The Trustees Of Boston University | System for assessing the efficacy of stored red blood cells using microvascular networks |
US8945913B2 (en) | 2012-12-17 | 2015-02-03 | Leukodx Ltd. | Kits, compositions and methods for detecting a biological condition |
US8961764B2 (en) | 2010-10-15 | 2015-02-24 | Lockheed Martin Corporation | Micro fluidic optic design |
US9005343B2 (en) | 2010-05-05 | 2015-04-14 | New Health Sciences, Inc. | Integrated leukocyte, oxygen and/or CO2 depletion, and plasma separation filter device |
US9056291B2 (en) | 2005-11-30 | 2015-06-16 | Micronics, Inc. | Microfluidic reactor system |
US9067207B2 (en) | 2009-06-04 | 2015-06-30 | University Of Virginia Patent Foundation | Optical approach for microfluidic DNA electrophoresis detection |
US9067004B2 (en) | 2011-03-28 | 2015-06-30 | New Health Sciences, Inc. | Method and system for removing oxygen and carbon dioxide during red cell blood processing using an inert carrier gas and manifold assembly |
US9073053B2 (en) | 1999-05-28 | 2015-07-07 | Cepheid | Apparatus and method for cell disruption |
US9132398B2 (en) | 2007-10-12 | 2015-09-15 | Rheonix, Inc. | Integrated microfluidic device and methods |
US9180449B2 (en) | 2012-06-12 | 2015-11-10 | Hach Company | Mobile water analysis |
US9182353B2 (en) | 2010-07-22 | 2015-11-10 | Hach Company | Lab-on-a-chip for alkalinity analysis |
US9199016B2 (en) | 2009-10-12 | 2015-12-01 | New Health Sciences, Inc. | System for extended storage of red blood cells and methods of use |
US9222623B2 (en) | 2013-03-15 | 2015-12-29 | Genmark Diagnostics, Inc. | Devices and methods for manipulating deformable fluid vessels |
US9260693B2 (en) | 2004-12-03 | 2016-02-16 | Cytonome/St, Llc | Actuation of parallel microfluidic arrays |
US9322054B2 (en) | 2012-02-22 | 2016-04-26 | Lockheed Martin Corporation | Microfluidic cartridge |
US9339025B2 (en) | 2010-08-25 | 2016-05-17 | New Health Sciences, Inc. | Method for enhancing red blood cell quality and survival during storage |
US20160137963A1 (en) * | 2013-06-28 | 2016-05-19 | Danmarks Tekniske Universitet | A Microfluidic Device with a Diffusion Barrier |
US9365822B2 (en) | 1997-12-31 | 2016-06-14 | Xy, Llc | System and method for sorting cells |
DE102015204235A1 (en) * | 2015-03-10 | 2016-09-15 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Fluidic structure with holding section and method for uniting two fluid volumes |
USD768872S1 (en) | 2012-12-12 | 2016-10-11 | Hach Company | Cuvette for a water analysis instrument |
US9498778B2 (en) | 2014-11-11 | 2016-11-22 | Genmark Diagnostics, Inc. | Instrument for processing cartridge for performing assays in a closed sample preparation and reaction system |
US9598722B2 (en) | 2014-11-11 | 2017-03-21 | Genmark Diagnostics, Inc. | Cartridge for performing assays in a closed sample preparation and reaction system |
US9789481B2 (en) | 1999-05-28 | 2017-10-17 | Cepheid | Device for extracting nucleic acid from a sample |
US9801784B2 (en) | 2015-04-23 | 2017-10-31 | New Health Sciences, Inc. | Anaerobic blood storage containers |
US9823252B2 (en) | 2004-12-03 | 2017-11-21 | Cytonome/St, Llc | Unitary cartridge for particle processing |
US9877476B2 (en) | 2013-02-28 | 2018-01-30 | New Health Sciences, Inc. | Gas depletion and gas addition devices for blood treatment |
US9895692B2 (en) | 2010-01-29 | 2018-02-20 | Micronics, Inc. | Sample-to-answer microfluidic cartridge |
US9957553B2 (en) | 2012-10-24 | 2018-05-01 | Genmark Diagnostics, Inc. | Integrated multiplex target analysis |
US9977037B2 (en) | 2012-05-22 | 2018-05-22 | New Health Sciences, Inc. | Capillary network devices and methods of use |
US10001496B2 (en) | 2007-01-29 | 2018-06-19 | Gearbox, Llc | Systems for allergen detection |
US10005080B2 (en) | 2014-11-11 | 2018-06-26 | Genmark Diagnostics, Inc. | Instrument and cartridge for performing assays in a closed sample preparation and reaction system employing electrowetting fluid manipulation |
US10058091B2 (en) | 2015-03-10 | 2018-08-28 | New Health Sciences, Inc. | Oxygen reduction disposable kits, devices and methods of use thereof |
US10065186B2 (en) | 2012-12-21 | 2018-09-04 | Micronics, Inc. | Fluidic circuits and related manufacturing methods |
US10087440B2 (en) | 2013-05-07 | 2018-10-02 | Micronics, Inc. | Device for preparation and analysis of nucleic acids |
US10107797B2 (en) | 2008-10-03 | 2018-10-23 | Micronics, Inc. | Microfluidic apparatus and methods for performing blood typing and crossmatching |
US10136635B2 (en) | 2010-05-05 | 2018-11-27 | New Health Sciences, Inc. | Irradiation of red blood cells and anaerobic storage |
US10190153B2 (en) | 2013-05-07 | 2019-01-29 | Micronics, Inc. | Methods for preparation of nucleic acid-containing samples using clay minerals and alkaline solutions |
US10296720B2 (en) | 2005-11-30 | 2019-05-21 | Gearbox Llc | Computational systems and methods related to nutraceuticals |
US10295545B2 (en) | 2013-11-14 | 2019-05-21 | Cambridge Enterprise Limited | Fluidic separation and detection |
US10386377B2 (en) | 2013-05-07 | 2019-08-20 | Micronics, Inc. | Microfluidic devices and methods for performing serum separation and blood cross-matching |
US10436713B2 (en) | 2012-12-21 | 2019-10-08 | Micronics, Inc. | Portable fluorescence detection system and microassay cartridge |
US10495656B2 (en) | 2012-10-24 | 2019-12-03 | Genmark Diagnostics, Inc. | Integrated multiplex target analysis |
US10518262B2 (en) | 2012-12-21 | 2019-12-31 | Perkinelmer Health Sciences, Inc. | Low elasticity films for microfluidic use |
US10583192B2 (en) | 2016-05-27 | 2020-03-10 | New Health Sciences, Inc. | Anaerobic blood storage and pathogen inactivation method |
US10610861B2 (en) | 2012-12-17 | 2020-04-07 | Accellix Ltd. | Systems, compositions and methods for detecting a biological condition |
USD881409S1 (en) | 2013-10-24 | 2020-04-14 | Genmark Diagnostics, Inc. | Biochip cartridge |
US10761094B2 (en) | 2012-12-17 | 2020-09-01 | Accellix Ltd. | Systems and methods for determining a chemical state |
US11013771B2 (en) | 2015-05-18 | 2021-05-25 | Hemanext Inc. | Methods for the storage of whole blood, and compositions thereof |
US11027278B2 (en) | 2002-04-17 | 2021-06-08 | Cytonome/St, Llc | Methods for controlling fluid flow in a microfluidic system |
US11105730B2 (en) | 2014-04-09 | 2021-08-31 | Nch Corporation | System and method for detecting biofilm growth in water systems |
WO2021180289A1 (en) | 2020-03-11 | 2021-09-16 | Fida Biosystems Aps | A method, an apparatus, an assembly and a system suitable for determining a characteristic property of a molecular interaction |
US11230695B2 (en) | 2002-09-13 | 2022-01-25 | Xy, Llc | Sperm cell processing and preservation systems |
US11284616B2 (en) | 2010-05-05 | 2022-03-29 | Hemanext Inc. | Irradiation of red blood cells and anaerobic storage |
WO2022147191A1 (en) * | 2020-12-31 | 2022-07-07 | Intuitive Surgical Operations, Inc. | Fluorescence evaluation apparatuses, systems, and methods |
US11633737B2 (en) * | 2016-04-20 | 2023-04-25 | Cellix Limited | Microfluidic chip for focussing a stream of particulate containing fluid |
US11959923B2 (en) | 2013-11-14 | 2024-04-16 | Cambridge Enterprise Limited | Fluidic separation and detection |
Families Citing this family (180)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5716852A (en) * | 1996-03-29 | 1998-02-10 | University Of Washington | Microfabricated diffusion-based chemical sensor |
US6454945B1 (en) * | 1995-06-16 | 2002-09-24 | University Of Washington | Microfabricated devices and methods |
ES2288760T3 (en) | 1996-04-25 | 2008-01-16 | Bioarray Solutions Ltd. | ELECTROCINETIC ASSEMBLY CONTROLLED BY LIGHT OF PARTICLES NEXT TO SURFACES. |
US6221654B1 (en) * | 1996-09-25 | 2001-04-24 | California Institute Of Technology | Method and apparatus for analysis and sorting of polynucleotides based on size |
US6833242B2 (en) * | 1997-09-23 | 2004-12-21 | California Institute Of Technology | Methods for detecting and sorting polynucleotides based on size |
US6540895B1 (en) | 1997-09-23 | 2003-04-01 | California Institute Of Technology | Microfabricated cell sorter for chemical and biological materials |
US7214298B2 (en) * | 1997-09-23 | 2007-05-08 | California Institute Of Technology | Microfabricated cell sorter |
US6109119A (en) * | 1998-02-27 | 2000-08-29 | Fffractionation, Llc | Sample focusing device and method |
CA2230653A1 (en) | 1998-02-27 | 1999-08-27 | The Governors Of The University Of Alberta | Microchip based enzymatic analysis |
KR20010052741A (en) | 1998-06-12 | 2001-06-25 | 야마모토 카즈모토 | Analyzer |
DE69907249T2 (en) | 1998-10-08 | 2004-01-29 | Astrazeneca Ab | MICROFABRICATED CELL INJECTOR |
GB9822242D0 (en) * | 1998-10-13 | 1998-12-09 | Zeneca Ltd | Device |
GB9822185D0 (en) | 1998-10-13 | 1998-12-02 | Zeneca Ltd | Device |
US6379973B1 (en) | 1999-03-05 | 2002-04-30 | The United States Of America As Represented By The Department Of Health And Human Services | Chromatographic separation apparatus and method |
US6602719B1 (en) | 1999-03-26 | 2003-08-05 | Idexx Laboratories, Inc. | Method and device for detecting analytes in fluids |
US6551842B1 (en) | 1999-03-26 | 2003-04-22 | Idexx Laboratories, Inc. | Method and device for detecting analytes in fluids |
US6511814B1 (en) | 1999-03-26 | 2003-01-28 | Idexx Laboratories, Inc. | Method and device for detecting analytes in fluids |
US20030022383A1 (en) * | 1999-04-06 | 2003-01-30 | Uab Research Foundation | Method for screening crystallization conditions in solution crystal growth |
ATE357656T1 (en) * | 1999-04-06 | 2007-04-15 | Univ Alabama Res Found | DEVICE FOR SCREENING CRYSTALIZATION CONDITIONS IN CRYSTAL GROWING SOLUTIONS |
US7247490B2 (en) * | 1999-04-06 | 2007-07-24 | Uab Research Foundation | Method for screening crystallization conditions in solution crystal growth |
US7250305B2 (en) * | 2001-07-30 | 2007-07-31 | Uab Research Foundation | Use of dye to distinguish salt and protein crystals under microcrystallization conditions |
US7214540B2 (en) * | 1999-04-06 | 2007-05-08 | Uab Research Foundation | Method for screening crystallization conditions in solution crystal growth |
US6649358B1 (en) * | 1999-06-01 | 2003-11-18 | Caliper Technologies Corp. | Microscale assays and microfluidic devices for transporter, gradient induced, and binding activities |
US20030124509A1 (en) * | 1999-06-03 | 2003-07-03 | Kenis Paul J.A. | Laminar flow patterning and articles made thereby |
DE19931901A1 (en) * | 1999-07-08 | 2001-01-11 | Basf Ag | Method and device for parallel analysis of colloidal particles with field flow fractionation |
US6268219B1 (en) | 1999-07-09 | 2001-07-31 | Orchid Biosciences, Inc. | Method and apparatus for distributing fluid in a microfluidic device |
WO2001011338A1 (en) * | 1999-08-06 | 2001-02-15 | Ulrik Darling Larsen | Particle characterisation apparatus |
US6569685B1 (en) | 1999-10-05 | 2003-05-27 | The Molecular Sciences Institute, Inc. | Protein fingerprint system and related methods |
US20050233459A1 (en) * | 2003-11-26 | 2005-10-20 | Melker Richard J | Marker detection method and apparatus to monitor drug compliance |
US20050037374A1 (en) * | 1999-11-08 | 2005-02-17 | Melker Richard J. | Combined nanotechnology and sensor technologies for simultaneous diagnosis and treatment |
JP4773019B2 (en) | 1999-11-08 | 2011-09-14 | ユニバーシティ オブ フロリダ リサーチ ファンデーション インコーポレーティッド | Marker detection method and apparatus for monitoring drug compliance |
AU2001240040A1 (en) * | 2000-03-03 | 2001-09-17 | California Institute Of Technology | Combinatorial array for nucleic acid analysis |
AU5121801A (en) * | 2000-03-31 | 2001-10-15 | Micronics Inc | Protein crystallization in microfluidic structures |
US7420659B1 (en) * | 2000-06-02 | 2008-09-02 | Honeywell Interantional Inc. | Flow control system of a cartridge |
US6520197B2 (en) | 2000-06-02 | 2003-02-18 | The Regents Of The University Of California | Continuous laminar fluid mixing in micro-electromechanical systems |
US7351376B1 (en) * | 2000-06-05 | 2008-04-01 | California Institute Of Technology | Integrated active flux microfluidic devices and methods |
ES2259666T3 (en) * | 2000-06-21 | 2006-10-16 | Bioarray Solutions Ltd | MOLECULAR ANALYSIS OF MULTIPLE ANALYTICS USING SERIES OF RANDOM PARTICLES WITH APPLICATION SPECIFICITY. |
US9709559B2 (en) | 2000-06-21 | 2017-07-18 | Bioarray Solutions, Ltd. | Multianalyte molecular analysis using application-specific random particle arrays |
US6829753B2 (en) * | 2000-06-27 | 2004-12-07 | Fluidigm Corporation | Microfluidic design automation method and system |
CA2415055A1 (en) * | 2000-08-03 | 2002-02-14 | Caliper Technologies Corporation | Methods and devices for high throughput fluid delivery |
EP1320752A2 (en) | 2000-09-18 | 2003-06-25 | President And Fellows of Harvard College | Differential treatment of selected parts of a single cell with different fluid components |
AU1189702A (en) * | 2000-10-13 | 2002-04-22 | Fluidigm Corp | Microfluidic device based sample injection system for analytical devices |
US20050011761A1 (en) * | 2000-10-31 | 2005-01-20 | Caliper Technologies Corp. | Microfluidic methods, devices and systems for in situ material concentration |
US20030057092A1 (en) * | 2000-10-31 | 2003-03-27 | Caliper Technologies Corp. | Microfluidic methods, devices and systems for in situ material concentration |
US20050054942A1 (en) * | 2002-01-22 | 2005-03-10 | Melker Richard J. | System and method for therapeutic drug monitoring |
US6981947B2 (en) * | 2002-01-22 | 2006-01-03 | University Of Florida Research Foundation, Inc. | Method and apparatus for monitoring respiratory gases during anesthesia |
US7104963B2 (en) * | 2002-01-22 | 2006-09-12 | University Of Florida Research Foundation, Inc. | Method and apparatus for monitoring intravenous (IV) drug concentration using exhaled breath |
AU2002243360A1 (en) * | 2000-12-26 | 2002-08-06 | C. Frederick Battrell | Microfluidic cartridge with integrated electronics |
CA2433350A1 (en) * | 2001-01-02 | 2002-08-01 | President And Fellows Of Harvard College | Method and apparatus for measurement of the sulfate concentration in air samples |
US7070681B2 (en) * | 2001-01-24 | 2006-07-04 | The Board Of Trustees Of The Leland Stanford Junior University | Electrokinetic instability micromixer |
US6681788B2 (en) | 2001-01-29 | 2004-01-27 | Caliper Technologies Corp. | Non-mechanical valves for fluidic systems |
US7670559B2 (en) | 2001-02-15 | 2010-03-02 | Caliper Life Sciences, Inc. | Microfluidic systems with enhanced detection systems |
DE60234572D1 (en) * | 2001-02-15 | 2010-01-14 | Caliper Life Sciences Inc | MICROFLUIDIC SYSTEMS WITH IMPROVED DETECTION SYSTEMS |
US7867776B2 (en) * | 2001-03-02 | 2011-01-11 | Caliper Life Sciences, Inc. | Priming module for microfluidic chips |
US20050196785A1 (en) * | 2001-03-05 | 2005-09-08 | California Institute Of Technology | Combinational array for nucleic acid analysis |
US7150999B1 (en) | 2001-03-09 | 2006-12-19 | Califer Life Sciences, Inc. | Process for filling microfluidic channels |
US20020159920A1 (en) * | 2001-04-03 | 2002-10-31 | Weigl Bernhard H. | Multiple redundant microfluidic structures cross reference to related applications |
US6742661B1 (en) * | 2001-04-03 | 2004-06-01 | Micronics, Inc. | Well-plate microfluidics |
US7314718B1 (en) * | 2001-04-03 | 2008-01-01 | Bioarray Solutions Ltd. | Method and apparatus for maintaining multiple planar fluid flows |
US7670429B2 (en) * | 2001-04-05 | 2010-03-02 | The California Institute Of Technology | High throughput screening of crystallization of materials |
AU2002307152A1 (en) * | 2001-04-06 | 2002-10-21 | California Institute Of Technology | Nucleic acid amplification utilizing microfluidic devices |
US20030040119A1 (en) * | 2001-04-11 | 2003-02-27 | The Regents Of The University Of Michigan | Separation devices and methods for separating particles |
AU2002310031A1 (en) * | 2001-05-23 | 2002-12-03 | University Of Florida | Method and apparatus for detecting illicit substances |
US7052854B2 (en) * | 2001-05-23 | 2006-05-30 | University Of Florida Research Foundation, Inc. | Application of nanotechnology and sensor technologies for ex-vivo diagnostics |
US7052468B2 (en) * | 2001-05-24 | 2006-05-30 | University Of Florida Research Foundation, Inc. | Method and apparatus for detecting environmental smoke exposure |
US7723123B1 (en) | 2001-06-05 | 2010-05-25 | Caliper Life Sciences, Inc. | Western blot by incorporating an affinity purification zone |
US20020187564A1 (en) * | 2001-06-08 | 2002-12-12 | Caliper Technologies Corp. | Microfluidic library analysis |
US6977163B1 (en) | 2001-06-13 | 2005-12-20 | Caliper Life Sciences, Inc. | Methods and systems for performing multiple reactions by interfacial mixing |
US7262063B2 (en) | 2001-06-21 | 2007-08-28 | Bio Array Solutions, Ltd. | Directed assembly of functional heterostructures |
US20030027225A1 (en) * | 2001-07-13 | 2003-02-06 | Caliper Technologies Corp. | Microfluidic devices and systems for separating components of a mixture |
KR20030008455A (en) * | 2001-07-18 | 2003-01-29 | 학교법인 포항공과대학교 | Sample pretreatment apparatus for mass spectrometry |
US7060171B1 (en) | 2001-07-31 | 2006-06-13 | Caliper Life Sciences, Inc. | Methods and systems for reducing background signal in assays |
US20070054408A1 (en) * | 2001-09-25 | 2007-03-08 | Cytonome, Inc. | Microfabricated two-pin system for biomolecule crystallization |
US7153699B2 (en) * | 2001-12-21 | 2006-12-26 | Cytonome, Inc. | Microfabricated two-pin system for biomolecule crystallization |
EP2722395B1 (en) | 2001-10-15 | 2018-12-19 | Bioarray Solutions Ltd | Multiplexed analysis of polymorphic loci by concurrent interrogation and enzyme-mediated detection |
US8440093B1 (en) | 2001-10-26 | 2013-05-14 | Fuidigm Corporation | Methods and devices for electronic and magnetic sensing of the contents of microfluidic flow channels |
US7247274B1 (en) | 2001-11-13 | 2007-07-24 | Caliper Technologies Corp. | Prevention of precipitate blockage in microfluidic channels |
EP1448798A1 (en) * | 2001-11-27 | 2004-08-25 | Gnothis Holding SA | Nanostructure, in particular for analysing individual molecules |
US7691333B2 (en) * | 2001-11-30 | 2010-04-06 | Fluidigm Corporation | Microfluidic device and methods of using same |
EP1463796B1 (en) * | 2001-11-30 | 2013-01-09 | Fluidigm Corporation | Microfluidic device and methods of using same |
EP1462805B1 (en) | 2001-12-14 | 2010-02-10 | Arkray, Inc. | Sample measuring device |
US20070167853A1 (en) * | 2002-01-22 | 2007-07-19 | Melker Richard J | System and method for monitoring health using exhaled breath |
US7223371B2 (en) * | 2002-03-14 | 2007-05-29 | Micronics, Inc. | Microfluidic channel network device |
US7312085B2 (en) * | 2002-04-01 | 2007-12-25 | Fluidigm Corporation | Microfluidic particle-analysis systems |
EP1499706A4 (en) | 2002-04-01 | 2010-11-03 | Fluidigm Corp | Microfluidic particle-analysis systems |
CA2480200A1 (en) * | 2002-04-02 | 2003-10-16 | Caliper Life Sciences, Inc. | Methods and apparatus for separation and isolation of components from a biological sample |
US20060127278A1 (en) * | 2002-04-26 | 2006-06-15 | Gast Alice P | System and method of measuring molecular interactions |
US20070026528A1 (en) * | 2002-05-30 | 2007-02-01 | Delucas Lawrence J | Method for screening crystallization conditions in solution crystal growth |
US7161356B1 (en) | 2002-06-05 | 2007-01-09 | Caliper Life Sciences, Inc. | Voltage/current testing equipment for microfluidic devices |
CA2489177C (en) * | 2002-06-11 | 2013-08-13 | Chempaq A/S | A disposable cartridge for characterizing particles suspended in a liquid |
US20060086309A1 (en) * | 2002-06-24 | 2006-04-27 | Fluiding Corporation | Recirculating fluidic network and methods for using the same |
US20040007672A1 (en) * | 2002-07-10 | 2004-01-15 | Delucas Lawrence J. | Method for distinguishing between biomolecule and non-biomolecule crystals |
US7699767B2 (en) | 2002-07-31 | 2010-04-20 | Arryx, Inc. | Multiple laminar flow-based particle and cellular separation with laser steering |
US11243494B2 (en) | 2002-07-31 | 2022-02-08 | Abs Global, Inc. | Multiple laminar flow-based particle and cellular separation with laser steering |
US20040038385A1 (en) * | 2002-08-26 | 2004-02-26 | Langlois Richard G. | System for autonomous monitoring of bioagents |
US6677593B1 (en) * | 2002-08-28 | 2004-01-13 | Ut-Battelle, Llc | Planar flow-by electrode capacitive electrospray ion source |
US6849459B2 (en) * | 2002-09-09 | 2005-02-01 | Cytonome, Inc. | Microfluidic chip for biomolecule crystallization |
AU2003266154B2 (en) * | 2002-09-11 | 2009-01-22 | Kreido Laboratories | Methods and apparatus for high-shear mixing and reacting of materials |
EP1551753A2 (en) | 2002-09-25 | 2005-07-13 | California Institute Of Technology | Microfluidic large scale integration |
JP5695287B2 (en) | 2002-10-02 | 2015-04-01 | カリフォルニア インスティテュート オブ テクノロジー | Nucleic acid analysis of microfluids |
US20060160134A1 (en) * | 2002-10-21 | 2006-07-20 | Melker Richard J | Novel application of biosensors for diagnosis and treatment of disease |
WO2004047007A1 (en) | 2002-11-15 | 2004-06-03 | Bioarray Solutions, Ltd. | Analysis, secure access to, and transmission of array images |
US7419638B2 (en) | 2003-01-14 | 2008-09-02 | Micronics, Inc. | Microfluidic devices for fluid manipulation and analysis |
KR20050118668A (en) * | 2003-01-21 | 2005-12-19 | 마이크로닉스 인코포레이티드. | Method and system for microfluidic manipulation, amplification and analysis of fluids, for example, bacteria assays and antiglobulin testing |
WO2004076038A1 (en) * | 2003-02-18 | 2004-09-10 | National Institute Of Advanced Industrial Science And Technology | Method and apparatus for separating molecules using micro-channel |
US20060076295A1 (en) * | 2004-03-15 | 2006-04-13 | The Trustees Of Columbia University In The City Of New York | Systems and methods of blood-based therapies having a microfluidic membraneless exchange device |
ATE510605T1 (en) * | 2003-03-14 | 2011-06-15 | Univ Columbia | SYSTEMS AND METHODS FOR BLOOD BASED THERAPY USING A MEMBRANELESS MICROFLUID EXCHANGE DEVICE |
US8828663B2 (en) * | 2005-03-18 | 2014-09-09 | Fluidigm Corporation | Thermal reaction device and method for using the same |
US7476363B2 (en) | 2003-04-03 | 2009-01-13 | Fluidigm Corporation | Microfluidic devices and methods of using same |
US7604965B2 (en) * | 2003-04-03 | 2009-10-20 | Fluidigm Corporation | Thermal reaction device and method for using the same |
US20050145496A1 (en) | 2003-04-03 | 2005-07-07 | Federico Goodsaid | Thermal reaction device and method for using the same |
US7666361B2 (en) * | 2003-04-03 | 2010-02-23 | Fluidigm Corporation | Microfluidic devices and methods of using same |
WO2005023391A2 (en) * | 2003-07-31 | 2005-03-17 | Arryx, Inc. | Multiple laminar flow-based particle and cellular separation with laser steering |
US7413712B2 (en) * | 2003-08-11 | 2008-08-19 | California Institute Of Technology | Microfluidic rotary flow reactor matrix |
EP3851030B1 (en) | 2003-09-11 | 2024-01-17 | Labrador Diagnostics LLC | Medical device for analyte monitoring |
WO2005029705A2 (en) * | 2003-09-18 | 2005-03-31 | Bioarray Solutions, Ltd. | Number coding for identification of subtypes of coded types of solid phase carriers |
ES2375962T3 (en) * | 2003-09-22 | 2012-03-07 | Bioarray Solutions Ltd | IMMOBILIZED SURFACE POLYELECTROLYTE WITH MULTIPLE FUNCTIONAL GROUPS ABLE TO JOIN COVALENTLY TO BIOMOLECULES. |
US20050089916A1 (en) * | 2003-10-28 | 2005-04-28 | Xiongwu Xia | Allele assignment and probe selection in multiplexed assays of polymorphic targets |
EP1692298A4 (en) * | 2003-10-28 | 2008-08-13 | Bioarray Solutions Ltd | Optimization of gene expression analysis using immobilized capture probes |
ES2533876T3 (en) | 2003-10-29 | 2015-04-15 | Bioarray Solutions Ltd | Multiplexed nucleic acid analysis by double stranded DNA fragmentation |
DE10353406A1 (en) * | 2003-11-14 | 2005-06-16 | INSTITUT FüR MIKROTECHNIK MAINZ GMBH | Process for the separation of chemical substances and / or particles, apparatus and their use |
US20050191757A1 (en) * | 2004-01-20 | 2005-09-01 | Melker Richard J. | Method and apparatus for detecting humans and human remains |
JP4461900B2 (en) * | 2004-05-10 | 2010-05-12 | 富士ゼロックス株式会社 | Method for feeding fine particle dispersion and liquid feeding device for fine particle dispersion |
US7363170B2 (en) * | 2004-07-09 | 2008-04-22 | Bio Array Solutions Ltd. | Transfusion registry network providing real-time interaction between users and providers of genetically characterized blood products |
JP4461941B2 (en) * | 2004-07-21 | 2010-05-12 | 富士ゼロックス株式会社 | Method for feeding fine particle dispersion and liquid feeding device for fine particle dispersion |
US7848889B2 (en) | 2004-08-02 | 2010-12-07 | Bioarray Solutions, Ltd. | Automated analysis of multiplexed probe-target interaction patterns: pattern matching and allele identification |
US20060062734A1 (en) * | 2004-09-20 | 2006-03-23 | Melker Richard J | Methods and systems for preventing diversion of prescription drugs |
AU2006204858A1 (en) * | 2005-01-13 | 2006-07-20 | Perkinelmer Health Sciences, Inc. | Microfluidic rare cell detection device |
AU2006212607B2 (en) | 2005-02-10 | 2010-12-09 | Koninklijke Philips Electronics N.V. | Dual sample cartridge and method for characterizing particle in liquid |
US8028566B2 (en) * | 2005-02-10 | 2011-10-04 | Chempaq A/S | Dual sample cartridge and method for characterizing particles in liquid |
US7314060B2 (en) * | 2005-04-23 | 2008-01-01 | Industrial Technology Research Institute | Fluid flow conducting module |
US20060264783A1 (en) * | 2005-05-09 | 2006-11-23 | Holmes Elizabeth A | Systems and methods for monitoring pharmacological parameters |
US20060257883A1 (en) * | 2005-05-10 | 2006-11-16 | Bjoraker David G | Detection and measurement of hematological parameters characterizing cellular blood components |
US8486629B2 (en) | 2005-06-01 | 2013-07-16 | Bioarray Solutions, Ltd. | Creation of functionalized microparticle libraries by oligonucleotide ligation or elongation |
JP4764969B2 (en) * | 2005-07-25 | 2011-09-07 | ローム株式会社 | Microchip measuring device |
EP2347825B1 (en) * | 2005-10-28 | 2016-10-19 | ARKRAY, Inc. | Analytical cartridge |
US20080178692A1 (en) * | 2007-01-29 | 2008-07-31 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Fluidic methods |
US20080179255A1 (en) * | 2007-01-29 | 2008-07-31 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Fluidic devices |
US20080241909A1 (en) * | 2007-03-27 | 2008-10-02 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Microfluidic chips for pathogen detection |
WO2007084392A2 (en) * | 2006-01-13 | 2007-07-26 | Micronics, Inc. | Electromagnetically actuated valves for use in microfluidic structures |
US8741230B2 (en) | 2006-03-24 | 2014-06-03 | Theranos, Inc. | Systems and methods of sample processing and fluid control in a fluidic system |
US11287421B2 (en) | 2006-03-24 | 2022-03-29 | Labrador Diagnostics Llc | Systems and methods of sample processing and fluid control in a fluidic system |
US8007999B2 (en) | 2006-05-10 | 2011-08-30 | Theranos, Inc. | Real-time detection of influenza virus |
CN101534917A (en) | 2006-05-22 | 2009-09-16 | 纽约市哥伦比亚大学理事会 | Systems and methods of microfluidic membraneless exchange using filtration of extraction fluid outlet streams |
JP4915690B2 (en) * | 2006-05-23 | 2012-04-11 | 国立大学法人電気通信大学 | Micro chemical chip equipment |
US7914460B2 (en) * | 2006-08-15 | 2011-03-29 | University Of Florida Research Foundation, Inc. | Condensate glucose analyzer |
US20080113391A1 (en) | 2006-11-14 | 2008-05-15 | Ian Gibbons | Detection and quantification of analytes in bodily fluids |
CA2580589C (en) * | 2006-12-19 | 2016-08-09 | Fio Corporation | Microfluidic detection system |
JP2007163504A (en) * | 2007-01-15 | 2007-06-28 | Microdent:Kk | Health measuring and examining system and method |
US20080181816A1 (en) * | 2007-01-29 | 2008-07-31 | Searete Llc, A Limited Liability Corporation | Systems for allergen detection |
US20090050569A1 (en) * | 2007-01-29 | 2009-02-26 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Fluidic methods |
US20080245740A1 (en) * | 2007-01-29 | 2008-10-09 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Fluidic methods |
US20090227005A1 (en) * | 2007-03-27 | 2009-09-10 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Methods for pathogen detection |
US8158430B1 (en) | 2007-08-06 | 2012-04-17 | Theranos, Inc. | Systems and methods of fluidic sample processing |
WO2009048533A2 (en) * | 2007-10-05 | 2009-04-16 | President And Fellows Of Harvard College | Reactions within microfluidic channels |
WO2009067071A1 (en) * | 2007-11-19 | 2009-05-28 | Carl Tyren | Method and device for differentiation of substances |
MX2010008591A (en) * | 2008-02-04 | 2010-08-30 | Univ Columbia | Fluid separation devices, systems and methods. |
US7995194B2 (en) * | 2008-04-02 | 2011-08-09 | Abbott Point Of Care, Inc. | Virtual separation of bound and free label in a ligand assay for performing immunoassays of biological fluids, including whole blood |
US8216526B2 (en) * | 2008-06-17 | 2012-07-10 | The United States of America, as represented by the Secretary of Commerce, The National Institute of Standards and Technology | Method and device for generating diffusive gradients in a microfluidic chamber |
US20100034704A1 (en) * | 2008-08-06 | 2010-02-11 | Honeywell International Inc. | Microfluidic cartridge channel with reduced bubble formation |
US8354080B2 (en) * | 2009-04-10 | 2013-01-15 | Canon U.S. Life Sciences, Inc. | Fluid interface cartridge for a microfluidic chip |
BR112012009196B1 (en) * | 2009-10-19 | 2021-03-30 | Labrador Diagnostics Llc | SYSTEM FOR MODELING THE PROGRESSION OF A DISEASE WITHIN A POPULATION |
WO2012040555A1 (en) * | 2010-09-26 | 2012-03-29 | Da Yu Enterprises, L.L.C. | Separation of analytes |
US10908066B2 (en) | 2010-11-16 | 2021-02-02 | 1087 Systems, Inc. | Use of vibrational spectroscopy for microfluidic liquid measurement |
WO2012178187A1 (en) | 2011-06-23 | 2012-12-27 | Paul Yager | Reagent patterning in capillarity-based analyzers and associated systems and methods |
JP2013220090A (en) * | 2012-04-19 | 2013-10-28 | Tohoku Univ | Drug screening method for use in eye disease treatment |
GB201219014D0 (en) * | 2012-10-23 | 2012-12-05 | Cambridge Entpr Ltd | Fluidic device |
EP2948249A1 (en) | 2013-01-22 | 2015-12-02 | University of Washington through its Center for Commercialization | Sequential delivery of fluid volumes and associated devices, systems and methods |
US8961904B2 (en) | 2013-07-16 | 2015-02-24 | Premium Genetics (Uk) Ltd. | Microfluidic chip |
US11796449B2 (en) | 2013-10-30 | 2023-10-24 | Abs Global, Inc. | Microfluidic system and method with focused energy apparatus |
GB2528632A (en) * | 2014-04-30 | 2016-02-03 | Cambridge Entpr Ltd | Fluidic analysis and separation |
GB201511651D0 (en) * | 2015-07-02 | 2015-08-19 | Cambridge Entpr Ltd | Viscosity measurements |
EP3352892A4 (en) * | 2015-09-22 | 2019-06-05 | Wyatt Technology Corporation | Method and apparatus to measure multiple signals from a liquid sample |
JP6903678B2 (en) | 2016-02-19 | 2021-07-14 | ペルキネルマー ヘルス サイエンシーズ, インコーポレイテッド | Microfluidic mixing devices and methods |
US20190261897A1 (en) * | 2017-11-28 | 2019-08-29 | Alan D. Kersey | Apparatus and method for assessment of cancer margin |
EP3796998A1 (en) | 2018-05-23 | 2021-03-31 | ABS Global, Inc. | Systems and methods for particle focusing in microchannels |
CN109187284B (en) * | 2018-09-07 | 2021-11-26 | 广东睿住住工科技有限公司 | Cement slurry testing equipment and method |
BR112021020390A2 (en) | 2019-04-18 | 2022-01-18 | Abs Global Inc | Cryoprotectant delivery system, cryopreservation system for delivering a cryoprotectant to a biological specimen, method for delivering a cryoprotectant to a biological specimen, delivery system, and method for preparing a biological specimen for cryopreservation |
US11628439B2 (en) | 2020-01-13 | 2023-04-18 | Abs Global, Inc. | Single-sheath microfluidic chip |
CN117153713B (en) * | 2023-10-25 | 2024-02-02 | 江苏惠达电子科技有限责任公司 | Method, system and equipment control method for detecting residual pollutants of frequency components |
Citations (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3449938A (en) * | 1967-08-03 | 1969-06-17 | Univ Utah | Method for separating and detecting fluid materials |
US3795489A (en) * | 1971-09-15 | 1974-03-05 | Ford Motor Co | Chemiluminescence reaction chamber |
US4147621A (en) * | 1977-06-28 | 1979-04-03 | University Of Utah | Method and apparatus for flow field-flow fractionation |
US4214981A (en) * | 1978-10-23 | 1980-07-29 | University Of Utah | Steric field-flow fractionation |
US4250026A (en) * | 1979-05-14 | 1981-02-10 | University Of Utah | Continuous steric FFF device for the size separation of particles |
US4683212A (en) * | 1982-09-30 | 1987-07-28 | Technicon Instruments Corporation | Random access single channel sheath stream apparatus |
US4726929A (en) * | 1985-01-25 | 1988-02-23 | Analytix, Inc. | Apparatus for measuring a chemical entity in a liquid |
US4737268A (en) * | 1986-03-18 | 1988-04-12 | University Of Utah | Thin channel split flow continuous equilibrium process and apparatus for particle fractionation |
US4756884A (en) * | 1985-08-05 | 1988-07-12 | Biotrack, Inc. | Capillary flow device |
US4830756A (en) * | 1988-07-11 | 1989-05-16 | University Of Utah | High speed separation of ultra-high molecular weight polymers by hyperlayer field-flow fractionation |
US4894146A (en) * | 1986-01-27 | 1990-01-16 | University Of Utah | Thin channel split flow process and apparatus for particle fractionation |
US4908112A (en) * | 1988-06-16 | 1990-03-13 | E. I. Du Pont De Nemours & Co. | Silicon semiconductor wafer for analyzing micronic biological samples |
EP0381501A2 (en) * | 1989-02-03 | 1990-08-08 | Eastman Kodak Company | Containment cuvette for PCR and method of use |
US5039426A (en) * | 1988-05-17 | 1991-08-13 | University Of Utah | Process for continuous particle and polymer separation in split-flow thin cells using flow-dependent lift forces |
EP0249701B1 (en) * | 1986-04-15 | 1992-01-29 | Three Bond Co., Ltd. | Cartridge for 2-part composition |
US5141651A (en) * | 1989-06-12 | 1992-08-25 | University Of Utah | Pinched channel inlet system for reduced relaxation effects and stopless flow injection in field-flow fractionation |
US5156039A (en) * | 1991-01-14 | 1992-10-20 | University Of Utah | Procedure for determining the size and size distribution of particles using sedimentation field-flow fractionation |
US5193688A (en) * | 1989-12-08 | 1993-03-16 | University Of Utah | Method and apparatus for hydrodynamic relaxation and sample concentration NIN field-flow fraction using permeable wall elements |
US5240618A (en) * | 1992-02-03 | 1993-08-31 | University Of Utah Research Foundation | Electrical field-flow fractionation using redox couple added to carrier fluid |
US5250263A (en) * | 1990-11-01 | 1993-10-05 | Ciba-Geigy Corporation | Apparatus for processing or preparing liquid samples for chemical analysis |
WO1993022053A1 (en) * | 1992-05-01 | 1993-11-11 | Trustees Of The University Of Pennsylvania | Microfabricated detection structures |
US5288463A (en) * | 1992-10-23 | 1994-02-22 | Eastman Kodak Company | Positive flow control in an unvented container |
US5304487A (en) * | 1992-05-01 | 1994-04-19 | Trustees Of The University Of Pennsylvania | Fluid handling in mesoscale analytical devices |
US5389524A (en) * | 1989-07-28 | 1995-02-14 | Kemisk Vaerk Koge A/S | Method and a system for quantitatively monitoring a chemical component dissolved in a liquid medium |
EP0645169A1 (en) * | 1993-09-23 | 1995-03-29 | Armand Ajdari | Improvements to methods and devices for separating particles from a fluid |
US5465849A (en) * | 1994-02-24 | 1995-11-14 | Doryokuro Kakunenryo Kaihatsu Jigyodan | Column and method for separating particles in accordance with their magnetic susceptibility |
US5480614A (en) * | 1993-03-16 | 1996-01-02 | Hitachi, Ltd. | Micro-reactor device for minute sample analysis |
WO1996004547A1 (en) * | 1994-08-01 | 1996-02-15 | Lockheed Martin Energy Systems, Inc. | Apparatus and method for performing microfluidic manipulations for chemical analysis and synthesis |
WO1996012541A1 (en) * | 1994-10-22 | 1996-05-02 | Central Research Laboratories Limited | Method and apparatus for diffusive transfer between immiscible fluids |
WO1996015576A1 (en) * | 1994-11-10 | 1996-05-23 | David Sarnoff Research Center, Inc. | Liquid distribution system |
WO1997000125A1 (en) * | 1995-06-16 | 1997-01-03 | Novartis Ag | Flow cell for the passive mixing of flowable substances |
WO1997002357A1 (en) * | 1995-06-29 | 1997-01-23 | Affymetrix, Inc. | Integrated nucleic acid diagnostic device |
US5599432A (en) * | 1993-11-11 | 1997-02-04 | Ciba-Geigy Corporation | Device and a method for the electrophoretic separation of fluid substance mixtures |
US5599503A (en) * | 1990-11-26 | 1997-02-04 | Ciba-Geigy Corporation | Detector cell |
US5637469A (en) * | 1992-05-01 | 1997-06-10 | Trustees Of The University Of Pennsylvania | Methods and apparatus for the detection of an analyte utilizing mesoscale flow systems |
US5716852A (en) * | 1996-03-29 | 1998-02-10 | University Of Washington | Microfabricated diffusion-based chemical sensor |
US5726751A (en) * | 1995-09-27 | 1998-03-10 | University Of Washington | Silicon microchannel optical flow cytometer |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0243310A3 (en) * | 1986-04-18 | 1989-10-18 | Ciba-Geigy Ag | Method for controlling and optimizing industrial processes |
US5389523A (en) * | 1988-05-31 | 1995-02-14 | The United States Of Americas, As Represented By The Secretary Of Commerce | Liposome immunoanalysis by flow injection assay |
US5149661A (en) * | 1988-06-08 | 1992-09-22 | Sarasep, Inc. | Fluid analysis with particulate reagent suspension |
DE4411266C2 (en) * | 1994-03-31 | 2001-05-17 | Danfoss As | Analysis method and device |
-
1996
- 1996-03-29 US US08/625,808 patent/US5716852A/en not_active Expired - Lifetime
-
1997
- 1997-03-31 EP EP97936008A patent/EP0890094B1/en not_active Expired - Lifetime
- 1997-03-31 JP JP53711297A patent/JP2001504936A/en not_active Ceased
- 1997-03-31 DE DE69724943T patent/DE69724943T2/en not_active Expired - Fee Related
- 1997-03-31 AU AU38777/97A patent/AU3877797A/en not_active Abandoned
- 1997-03-31 US US08/829,679 patent/US5972710A/en not_active Expired - Lifetime
- 1997-03-31 WO PCT/US1997/005245 patent/WO1997039338A1/en active IP Right Grant
-
2007
- 2007-05-08 JP JP2007124013A patent/JP2007292773A/en active Pending
Patent Citations (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3449938A (en) * | 1967-08-03 | 1969-06-17 | Univ Utah | Method for separating and detecting fluid materials |
US3795489A (en) * | 1971-09-15 | 1974-03-05 | Ford Motor Co | Chemiluminescence reaction chamber |
US4147621A (en) * | 1977-06-28 | 1979-04-03 | University Of Utah | Method and apparatus for flow field-flow fractionation |
US4214981A (en) * | 1978-10-23 | 1980-07-29 | University Of Utah | Steric field-flow fractionation |
US4250026A (en) * | 1979-05-14 | 1981-02-10 | University Of Utah | Continuous steric FFF device for the size separation of particles |
US4683212A (en) * | 1982-09-30 | 1987-07-28 | Technicon Instruments Corporation | Random access single channel sheath stream apparatus |
US4726929A (en) * | 1985-01-25 | 1988-02-23 | Analytix, Inc. | Apparatus for measuring a chemical entity in a liquid |
US4756884A (en) * | 1985-08-05 | 1988-07-12 | Biotrack, Inc. | Capillary flow device |
US4894146A (en) * | 1986-01-27 | 1990-01-16 | University Of Utah | Thin channel split flow process and apparatus for particle fractionation |
US4737268A (en) * | 1986-03-18 | 1988-04-12 | University Of Utah | Thin channel split flow continuous equilibrium process and apparatus for particle fractionation |
EP0249701B1 (en) * | 1986-04-15 | 1992-01-29 | Three Bond Co., Ltd. | Cartridge for 2-part composition |
US5039426A (en) * | 1988-05-17 | 1991-08-13 | University Of Utah | Process for continuous particle and polymer separation in split-flow thin cells using flow-dependent lift forces |
US4908112A (en) * | 1988-06-16 | 1990-03-13 | E. I. Du Pont De Nemours & Co. | Silicon semiconductor wafer for analyzing micronic biological samples |
US4830756A (en) * | 1988-07-11 | 1989-05-16 | University Of Utah | High speed separation of ultra-high molecular weight polymers by hyperlayer field-flow fractionation |
EP0381501A2 (en) * | 1989-02-03 | 1990-08-08 | Eastman Kodak Company | Containment cuvette for PCR and method of use |
US5141651A (en) * | 1989-06-12 | 1992-08-25 | University Of Utah | Pinched channel inlet system for reduced relaxation effects and stopless flow injection in field-flow fractionation |
US5389524A (en) * | 1989-07-28 | 1995-02-14 | Kemisk Vaerk Koge A/S | Method and a system for quantitatively monitoring a chemical component dissolved in a liquid medium |
US5193688A (en) * | 1989-12-08 | 1993-03-16 | University Of Utah | Method and apparatus for hydrodynamic relaxation and sample concentration NIN field-flow fraction using permeable wall elements |
US5250263A (en) * | 1990-11-01 | 1993-10-05 | Ciba-Geigy Corporation | Apparatus for processing or preparing liquid samples for chemical analysis |
US5599503A (en) * | 1990-11-26 | 1997-02-04 | Ciba-Geigy Corporation | Detector cell |
US5156039A (en) * | 1991-01-14 | 1992-10-20 | University Of Utah | Procedure for determining the size and size distribution of particles using sedimentation field-flow fractionation |
US5240618A (en) * | 1992-02-03 | 1993-08-31 | University Of Utah Research Foundation | Electrical field-flow fractionation using redox couple added to carrier fluid |
WO1993022053A1 (en) * | 1992-05-01 | 1993-11-11 | Trustees Of The University Of Pennsylvania | Microfabricated detection structures |
US5637469A (en) * | 1992-05-01 | 1997-06-10 | Trustees Of The University Of Pennsylvania | Methods and apparatus for the detection of an analyte utilizing mesoscale flow systems |
US5635358A (en) * | 1992-05-01 | 1997-06-03 | Trustees Of The University Of Pennsylvania | Fluid handling methods for use in mesoscale analytical devices |
US5304487A (en) * | 1992-05-01 | 1994-04-19 | Trustees Of The University Of Pennsylvania | Fluid handling in mesoscale analytical devices |
US5288463A (en) * | 1992-10-23 | 1994-02-22 | Eastman Kodak Company | Positive flow control in an unvented container |
US5480614A (en) * | 1993-03-16 | 1996-01-02 | Hitachi, Ltd. | Micro-reactor device for minute sample analysis |
EP0645169A1 (en) * | 1993-09-23 | 1995-03-29 | Armand Ajdari | Improvements to methods and devices for separating particles from a fluid |
US5599432A (en) * | 1993-11-11 | 1997-02-04 | Ciba-Geigy Corporation | Device and a method for the electrophoretic separation of fluid substance mixtures |
US5465849A (en) * | 1994-02-24 | 1995-11-14 | Doryokuro Kakunenryo Kaihatsu Jigyodan | Column and method for separating particles in accordance with their magnetic susceptibility |
WO1996004547A1 (en) * | 1994-08-01 | 1996-02-15 | Lockheed Martin Energy Systems, Inc. | Apparatus and method for performing microfluidic manipulations for chemical analysis and synthesis |
WO1996012541A1 (en) * | 1994-10-22 | 1996-05-02 | Central Research Laboratories Limited | Method and apparatus for diffusive transfer between immiscible fluids |
WO1996015576A1 (en) * | 1994-11-10 | 1996-05-23 | David Sarnoff Research Center, Inc. | Liquid distribution system |
WO1997000125A1 (en) * | 1995-06-16 | 1997-01-03 | Novartis Ag | Flow cell for the passive mixing of flowable substances |
WO1997002357A1 (en) * | 1995-06-29 | 1997-01-23 | Affymetrix, Inc. | Integrated nucleic acid diagnostic device |
US5726751A (en) * | 1995-09-27 | 1998-03-10 | University Of Washington | Silicon microchannel optical flow cytometer |
US5716852A (en) * | 1996-03-29 | 1998-02-10 | University Of Washington | Microfabricated diffusion-based chemical sensor |
Non-Patent Citations (38)
Title |
---|
Brody, J.P. and Yager, P. (1996), "Low Reynolds Number Micro-Fluidic Devices," Solid State Sensor & Actuator Workshop, Hilton Head, SC, Jun. 2-6, 1996, pp. 105-108. |
Brody, J.P. and Yager, P. (1996), Low Reynolds Number Micro Fluidic Devices, Solid State Sensor & Actuator Workshop, Hilton Head, SC, Jun. 2 6, 1996, pp. 105 108. * |
Chmelik, Josef, "Isoelectric focusing field-flow fractionation" Journal of Chromatography 545, No. 2 (1991). |
Chmelik, Josef, Isoelectric focusing field flow fractionation Journal of Chromatography 545, No. 2 (1991). * |
Faucheux, L.P. et al. (1995), "Optical Thermal Ratchet," Phys. Rev. Lett. 74:1504-1507. |
Faucheux, L.P. et al. (1995), Optical Thermal Ratchet, Phys. Rev. Lett. 74:1504 1507. * |
Giddings, J.C. (1985), "Optimized Field-Flow Fractionation System Based on Dual Stream Splitters," Anal. Chem. 57:945-947. |
Giddings, J.C. (1985), Optimized Field Flow Fractionation System Based on Dual Stream Splitters, Anal. Chem. 57:945 947. * |
Giddings, J.C. (1993), "Field-Flow Franctionation: Analysis of Macromolecular, Colloidal and Particulate Materials," Science 260:1456-1465. |
Giddings, J.C. (1993), Field Flow Franctionation: Analysis of Macromolecular, Colloidal and Particulate Materials, Science 260:1456 1465. * |
Giddings, J.C. et al. (1983), "Outlet Stream Splitting for Sample Concentration in Field-Flow Fractionation," Separation Science and Technology 18:293-306. |
Giddings, J.C. et al. (1983), Outlet Stream Splitting for Sample Concentration in Field Flow Fractionation, Separation Science and Technology 18:293 306. * |
Leff, H.S. and Rex, A.F. (1990), "Resource letter MD-1: Maxwell's demon," Am. J. Phys. 58:201-209. |
Leff, H.S. and Rex, A.F. (1990), Resource letter MD 1: Maxwell s demon, Am. J. Phys. 58:201 209. * |
Manz, A. et al., "Planar Chips Technology for Miniaturization of Separation Systems: A Developing Perspective in Chemical Monitoring, " (1993) Advances in Chromatography 33:2-66. |
Manz, A. et al., Planar Chips Technology for Miniaturization of Separation Systems: A Developing Perspective in Chemical Monitoring, (1993) Advances in Chromatography 33:2 66. * |
Petersen, K.E. (1982), "Silicon as a Mechanical Material," Proc. IEEE 70(5):420-457. |
Petersen, K.E. (1982), Silicon as a Mechanical Material, Proc. IEEE 70(5):420 457. * |
Reisman, A. et al. (1979), "The Controlled Etching of Silicon in Catalyzed Ethylenediamine-Pyrocatechol-Water Solutions," J. Electrochem. Soc. 126:1406-1415. |
Reisman, A. et al. (1979), The Controlled Etching of Silicon in Catalyzed Ethylenediamine Pyrocatechol Water Solutions, J. Electrochem. Soc. 126:1406 1415. * |
Rousselet, J. et al. (1994), "Directional motion of brownian particles induced by a periodic asymmetric potential," Nature 370:446-448. |
Rousselet, J. et al. (1994), Directional motion of brownian particles induced by a periodic asymmetric potential, Nature 370:446 448. * |
Shoji, S. and Esashi, M. (1994), "Microflow devices and systems," J. Micromech. and Microeng. 4:157-171. |
Shoji, S. and Esashi, M. (1994), Microflow devices and systems, J. Micromech. and Microeng. 4:157 171. * |
Verpoorte, E.M.J. et al., "Three-dimensional micro flow manifolds for miniaturized chemical analysis systems," (1994) J. Micromech. Microeng. 4:246-256. |
Verpoorte, E.M.J. et al., Three dimensional micro flow manifolds for miniaturized chemical analysis systems, (1994) J. Micromech. Microeng. 4:246 256. * |
Wallis, G. and Pomerantz, D.I. (1969), "Field Assisted Glass-Metal Sealing," J. Appl. Phys. 40:3946-3949. |
Wallis, G. and Pomerantz, D.I. (1969), Field Assisted Glass Metal Sealing, J. Appl. Phys. 40:3946 3949. * |
Weigl, B. H. et al. (1996), "Diffusion-Based Opitcal Chemical Detection in Silicon Flow Structures," Analytical Methods & Instrumentation Special Issue μTAS 96, pp. 174-184. |
Weigl, B. H. et al. (1996), Diffusion Based Opitcal Chemical Detection in Silicon Flow Structures, Analytical Methods & Instrumentation Special Issue TAS 96, pp. 174 184. * |
Weigl, B.H. and Yager, P. (1996), "Silicon-Microfabricated Diffusion-Based Optical Chemical Sensor," presented at Europtrode Conference, Zurich, Switzerland, Apr. 2-3, 1996. |
Weigl, B.H. and Yager, P. (1996), Silicon Microfabricated Diffusion Based Optical Chemical Sensor, presented at Europtrode Conference, Zurich, Switzerland, Apr. 2 3, 1996. * |
Weigl, B.H. et al. (1996), "Rapid sequential chemical analysis in microfabricated flow structures using multiple fluorescent reporter beads," μTAS 96 (Nov '96). |
Weigl, B.H. et al. (1996), Rapid sequential chemical analysis in microfabricated flow structures using multiple fluorescent reporter beads, TAS 96 (Nov 96). * |
Weigl, B.H. et al. (1997), "Fluorescence and absorbance analyte sensing in whole blood and plasma based on diffusion separation in silicon-microfabricated flow structures," SPIE Proceedings, J. Lakowitz (ed.), Fluorescence Sensing Technology III (Feb. 9-11, 1997). |
Weigl, B.H. et al. (1997), Fluorescence and absorbance analyte sensing in whole blood and plasma based on diffusion separation in silicon microfabricated flow structures, SPIE Proceedings, J. Lakowitz (ed.), Fluorescence Sensing Technology III (Feb. 9 11, 1997). * |
Williams, P.S. et al. (1992), "Continuous SPLITT Fractionation Based on a Diffusion Mechanism," Ind. Eng. Chem. Res. 31:2172-2181. |
Williams, P.S. et al. (1992), Continuous SPLITT Fractionation Based on a Diffusion Mechanism, Ind. Eng. Chem. Res. 31:2172 2181. * |
Cited By (402)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060115905A1 (en) * | 1996-03-29 | 2006-06-01 | University Of Washington | Microscale diffusion immunoassay in hydrogels |
US6582963B1 (en) | 1996-03-29 | 2003-06-24 | University Of Washington | Simultaneous analyte determination and reference balancing in reference T-sensor devices |
US20030124619A1 (en) * | 1996-03-29 | 2003-07-03 | Weigl Bernhard H. | Microscale diffusion immunoassay |
US6171865B1 (en) * | 1996-03-29 | 2001-01-09 | University Of Washington | Simultaneous analyte determination and reference balancing in reference T-sensor devices |
US7271007B2 (en) | 1996-03-29 | 2007-09-18 | University Of Washington | Microscale diffusion immunoassay |
US6541213B1 (en) * | 1996-03-29 | 2003-04-01 | University Of Washington | Microscale diffusion immunoassay |
US7929137B2 (en) | 1997-01-31 | 2011-04-19 | Xy, Llc | Optical apparatus |
US6159739A (en) * | 1997-03-26 | 2000-12-12 | University Of Washington | Device and method for 3-dimensional alignment of particles in microfabricated flow channels |
US6134950A (en) * | 1997-06-13 | 2000-10-24 | University Of Washington | Method for determining concentration of a laminar sample stream |
US6893879B2 (en) | 1997-08-13 | 2005-05-17 | Cepheid | Method for separating analyte from a sample |
US6368871B1 (en) * | 1997-08-13 | 2002-04-09 | Cepheid | Non-planar microstructures for manipulation of fluid samples |
US7135144B2 (en) | 1997-08-13 | 2006-11-14 | Cepheid | Method for the manipulation of a fluid sample |
US20020175079A1 (en) * | 1997-08-13 | 2002-11-28 | Cepheid | Device and method for the manipulation of a fluid sample |
US6297061B1 (en) * | 1997-09-26 | 2001-10-02 | University Of Washington | Simultaneous particle separation and chemical reaction |
US6221677B1 (en) * | 1997-09-26 | 2001-04-24 | University Of Washington | Simultaneous particle separation and chemical reaction |
US6277641B1 (en) * | 1997-09-26 | 2001-08-21 | University Of Washington | Methods for analyzing the presence and concentration of multiple analytes using a diffusion-based chemical sensor |
US20050194316A1 (en) * | 1997-12-24 | 2005-09-08 | Cepheid | Method for separating analyte from a sample |
US6440725B1 (en) | 1997-12-24 | 2002-08-27 | Cepheid | Integrated fluid manipulation cartridge |
US7569346B2 (en) | 1997-12-24 | 2009-08-04 | Cepheid | Method for separating analyte from a sample |
US9365822B2 (en) | 1997-12-31 | 2016-06-14 | Xy, Llc | System and method for sorting cells |
US9422523B2 (en) | 1997-12-31 | 2016-08-23 | Xy, Llc | System and method for sorting cells |
US20090263284A1 (en) * | 1998-01-20 | 2009-10-22 | Ge Healthcare Bio-Sciences Ab | Method and device for laminar flow on a sensing surface |
US7811515B2 (en) * | 1998-01-20 | 2010-10-12 | Ge Healthcare Bio-Sciences Ab | Method and device for laminar flow on a sensing surface |
US6576194B1 (en) * | 1998-05-18 | 2003-06-10 | University Of Washington | Sheath flow assembly |
US6712925B1 (en) | 1998-05-18 | 2004-03-30 | University Of Washington | Method of making a liquid analysis cartridge |
US6852284B1 (en) | 1998-05-18 | 2005-02-08 | University Of Washington | Liquid analysis cartridge |
US20060127275A1 (en) * | 1998-05-18 | 2006-06-15 | University Of Washington | Liquid analysis cartridge |
US7226562B2 (en) | 1998-05-18 | 2007-06-05 | University Of Washington | Liquid analysis cartridge |
US6830729B1 (en) | 1998-05-18 | 2004-12-14 | University Of Washington | Sample analysis instrument |
US6843963B1 (en) * | 1998-05-25 | 2005-01-18 | Herbert Peter Jennissen | Flow-through shear analyzer for biologically active molecules in liquid layers on surfaces |
US6404493B1 (en) | 1998-10-09 | 2002-06-11 | University Of Washington | Dual large angle light scattering detection |
US8247176B2 (en) | 1998-12-24 | 2012-08-21 | Cepheid | Method for separating an analyte from a sample |
US6987018B2 (en) | 1998-12-24 | 2006-01-17 | Cepheid | Container for holding cells or viruses for disruption |
US8592157B2 (en) | 1998-12-24 | 2013-11-26 | Cepheid | Method for separating an analyte from a sample |
US7914994B2 (en) | 1998-12-24 | 2011-03-29 | Cepheid | Method for separating an analyte from a sample |
US20100068706A1 (en) * | 1998-12-24 | 2010-03-18 | Cepheid | Method for separating an analyte from a sample |
US6887693B2 (en) | 1998-12-24 | 2005-05-03 | Cepheid | Device and method for lysing cells, spores, or microorganisms |
US6592821B1 (en) * | 1999-05-17 | 2003-07-15 | Caliper Technologies Corp. | Focusing of microparticles in microfluidic systems |
WO2000070080A1 (en) * | 1999-05-17 | 2000-11-23 | Caliper Technologies Corp. | Focusing of microparticles in microfluidic systems |
US6506609B1 (en) | 1999-05-17 | 2003-01-14 | Caliper Technologies Corp. | Focusing of microparticles in microfluidic systems |
WO2000072020A1 (en) * | 1999-05-21 | 2000-11-30 | University Of Washington | Microscale diffusion immunoassay |
US9073053B2 (en) | 1999-05-28 | 2015-07-07 | Cepheid | Apparatus and method for cell disruption |
US20060030038A1 (en) * | 1999-05-28 | 2006-02-09 | Chpheid | Apparatus and method for cell disruption |
US9789481B2 (en) | 1999-05-28 | 2017-10-17 | Cepheid | Device for extracting nucleic acid from a sample |
US20040200909A1 (en) * | 1999-05-28 | 2004-10-14 | Cepheid | Apparatus and method for cell disruption |
US9943848B2 (en) | 1999-05-28 | 2018-04-17 | Cepheid | Apparatus and method for cell disruption |
US8268603B2 (en) | 1999-05-28 | 2012-09-18 | Cepheid | Apparatus and method for cell disruption |
US20040256230A1 (en) * | 1999-06-03 | 2004-12-23 | University Of Washington | Microfluidic devices for transverse electrophoresis and isoelectric focusing |
US6664104B2 (en) | 1999-06-25 | 2003-12-16 | Cepheid | Device incorporating a microfluidic chip for separating analyte from a sample |
US20020045246A1 (en) * | 1999-06-25 | 2002-04-18 | Cepheid | Device for lysing cells, spores, or microorganisms |
US6878540B2 (en) | 1999-06-25 | 2005-04-12 | Cepheid | Device for lysing cells, spores, or microorganisms |
US6613580B1 (en) * | 1999-07-06 | 2003-09-02 | Caliper Technologies Corp. | Microfluidic systems and methods for determining modulator kinetics |
US6858185B1 (en) * | 1999-08-25 | 2005-02-22 | Caliper Life Sciences, Inc. | Dilutions in high throughput systems with a single vacuum source |
US6210986B1 (en) * | 1999-09-23 | 2001-04-03 | Sandia Corporation | Microfluidic channel fabrication method |
US6743399B1 (en) * | 1999-10-08 | 2004-06-01 | Micronics, Inc. | Pumpless microfluidics |
US7820425B2 (en) | 1999-11-24 | 2010-10-26 | Xy, Llc | Method of cryopreserving selected sperm cells |
US6408884B1 (en) | 1999-12-15 | 2002-06-25 | University Of Washington | Magnetically actuated fluid handling devices for microfluidic applications |
US6415821B2 (en) | 1999-12-15 | 2002-07-09 | University Of Washington | Magnetically actuated fluid handling devices for microfluidic applications |
US6431476B1 (en) | 1999-12-21 | 2002-08-13 | Cepheid | Apparatus and method for rapid ultrasonic disruption of cells or viruses |
US6488896B2 (en) * | 2000-03-14 | 2002-12-03 | Micronics, Inc. | Microfluidic analysis cartridge |
US20010042712A1 (en) * | 2000-05-24 | 2001-11-22 | Battrell C. Frederick | Microfluidic concentration gradient loop |
US8815521B2 (en) | 2000-05-30 | 2014-08-26 | Cepheid | Apparatus and method for cell disruption |
US20060263888A1 (en) * | 2000-06-02 | 2006-11-23 | Honeywell International Inc. | Differential white blood count on a disposable card |
US7553453B2 (en) | 2000-06-02 | 2009-06-30 | Honeywell International Inc. | Assay implementation in a microfluidic format |
US20060256336A1 (en) * | 2000-08-02 | 2006-11-16 | Fritz Bernard S | Optical alignment detection system |
US20050134850A1 (en) * | 2000-08-02 | 2005-06-23 | Tom Rezachek | Optical alignment system for flow cytometry |
US7978329B2 (en) | 2000-08-02 | 2011-07-12 | Honeywell International Inc. | Portable scattering and fluorescence cytometer |
US7215425B2 (en) | 2000-08-02 | 2007-05-08 | Honeywell International Inc. | Optical alignment for flow cytometry |
US7312870B2 (en) | 2000-08-02 | 2007-12-25 | Honeywell International Inc. | Optical alignment detection system |
US6970245B2 (en) | 2000-08-02 | 2005-11-29 | Honeywell International Inc. | Optical alignment detection system |
US20050078299A1 (en) * | 2000-08-02 | 2005-04-14 | Fritz Bernard S. | Dual use detectors for flow cytometry |
US20030142291A1 (en) * | 2000-08-02 | 2003-07-31 | Aravind Padmanabhan | Portable scattering and fluorescence cytometer |
US6597438B1 (en) | 2000-08-02 | 2003-07-22 | Honeywell International Inc. | Portable flow cytometry |
US20050105077A1 (en) * | 2000-08-02 | 2005-05-19 | Aravind Padmanabhan | Miniaturized cytometer for detecting multiple species in a sample |
US20050118723A1 (en) * | 2000-08-02 | 2005-06-02 | Aravind Padmanabhan | Optical detection system with polarizing beamsplitter |
US20050122522A1 (en) * | 2000-08-02 | 2005-06-09 | Aravind Padmanabhan | Optical detection system for flow cytometry |
US7277166B2 (en) | 2000-08-02 | 2007-10-02 | Honeywell International Inc. | Cytometer analysis cartridge optical configuration |
US7471394B2 (en) | 2000-08-02 | 2008-12-30 | Honeywell International Inc. | Optical detection system with polarizing beamsplitter |
US7911617B2 (en) | 2000-08-02 | 2011-03-22 | Honeywell International Inc. | Miniaturized cytometer for detecting multiple species in a sample |
US6549275B1 (en) | 2000-08-02 | 2003-04-15 | Honeywell International Inc. | Optical detection system for flow cytometry |
US20030058445A1 (en) * | 2000-08-02 | 2003-03-27 | Fritz Bernard S. | Optical alignment detection system |
US7630063B2 (en) | 2000-08-02 | 2009-12-08 | Honeywell International Inc. | Miniaturized cytometer for detecting multiple species in a sample |
US7671987B2 (en) | 2000-08-02 | 2010-03-02 | Honeywell International Inc | Optical detection system for flow cytometry |
US6382228B1 (en) | 2000-08-02 | 2002-05-07 | Honeywell International Inc. | Fluid driving system for flow cytometry |
US20050243304A1 (en) * | 2000-08-02 | 2005-11-03 | Honeywell International Inc. | Cytometer analysis cartridge optical configuration |
US7061595B2 (en) | 2000-08-02 | 2006-06-13 | Honeywell International Inc. | Miniaturized flow controller with closed loop regulation |
US7016022B2 (en) | 2000-08-02 | 2006-03-21 | Honeywell International Inc. | Dual use detectors for flow cytometry |
US7027683B2 (en) | 2000-08-15 | 2006-04-11 | Nanostream, Inc. | Optical devices with fluidic systems |
WO2002023161A1 (en) * | 2000-09-18 | 2002-03-21 | University Of Washington | Microfluidic devices for rotational manipulation of the fluidic interface between multiple flow streams |
US7011791B2 (en) | 2000-09-18 | 2006-03-14 | University Of Washington | Microfluidic devices for rotational manipulation of the fluidic interface between multiple flow streams |
EP1339496A2 (en) * | 2000-11-06 | 2003-09-03 | The Government of the United States of America, as represented by the Secretary of Health and Human Services | Sample delivery system with laminar mixing for microvolume biosensing |
EP1339496A4 (en) * | 2000-11-06 | 2004-10-27 | Us Gov Health & Human Serv | Sample delivery system with laminar mixing for microvolume biosensing |
US8652769B2 (en) | 2000-11-29 | 2014-02-18 | Xy, Llc | Methods for separating frozen-thawed spermatozoa into X-chromosome bearing and Y-chromosome bearing populations |
US7771921B2 (en) | 2000-11-29 | 2010-08-10 | Xy, Llc | Separation systems of frozen-thawed spermatozoa into X-chromosome bearing and Y-chromosome bearing populations |
US8137967B2 (en) | 2000-11-29 | 2012-03-20 | Xy, Llc | In-vitro fertilization systems with spermatozoa separated into X-chromosome and Y-chromosome bearing populations |
US9879221B2 (en) | 2000-11-29 | 2018-01-30 | Xy, Llc | Method of in-vitro fertilization with spermatozoa separated into X-chromosome and Y-chromosome bearing populations |
US7713687B2 (en) | 2000-11-29 | 2010-05-11 | Xy, Inc. | System to separate frozen-thawed spermatozoa into x-chromosome bearing and y-chromosome bearing populations |
US20020127740A1 (en) * | 2001-03-06 | 2002-09-12 | Ho Winston Z. | Quantitative microfluidic biochip and method of use |
US9146221B2 (en) | 2001-03-24 | 2015-09-29 | Aviva Biosciences Corporation | High-density ion transport measurement biochip devices and methods |
WO2002077259A3 (en) * | 2001-03-24 | 2002-11-14 | Aviva Biosciences Corp | Biochips including ion transport detecting structures and methods of use |
US7968305B2 (en) | 2001-03-24 | 2011-06-28 | Aviva Biosciences Corporation | Biochips including ion transport detecting structures and methods of use |
US20050058990A1 (en) * | 2001-03-24 | 2005-03-17 | Antonio Guia | Biochip devices for ion transport measurement, methods of manufacture, and methods of use |
US20090209029A1 (en) * | 2001-03-24 | 2009-08-20 | Antonio Guia | High-density ion transport measurement biochip devices and methods |
US20060029955A1 (en) * | 2001-03-24 | 2006-02-09 | Antonio Guia | High-density ion transport measurement biochip devices and methods |
US20050196746A1 (en) * | 2001-03-24 | 2005-09-08 | Jia Xu | High-density ion transport measurement biochip devices and methods |
WO2002077259A2 (en) * | 2001-03-24 | 2002-10-03 | Aviva Biosciences Corporation | Biochips including ion transport detecting structures and methods of use |
US20020182627A1 (en) * | 2001-03-24 | 2002-12-05 | Xiaobo Wang | Biochips including ion transport detecting strucutres and methods of use |
US20050009101A1 (en) * | 2001-05-17 | 2005-01-13 | Motorola, Inc. | Microfluidic devices comprising biochannels |
US7262838B2 (en) | 2001-06-29 | 2007-08-28 | Honeywell International Inc. | Optical detection system for flow cytometry |
US20070188737A1 (en) * | 2001-06-29 | 2007-08-16 | Honeywell International Inc. | Optical detection system for flow cytometry |
US6700130B2 (en) | 2001-06-29 | 2004-03-02 | Honeywell International Inc. | Optical detection system for flow cytometry |
US20040145725A1 (en) * | 2001-06-29 | 2004-07-29 | Fritz Bernard S. | Optical detection system for flow cytometry |
US7486387B2 (en) | 2001-06-29 | 2009-02-03 | Honeywell International Inc. | Optical detection system for flow cytometry |
US6825127B2 (en) | 2001-07-24 | 2004-11-30 | Zarlink Semiconductor Inc. | Micro-fluidic devices |
WO2003020886A2 (en) * | 2001-08-29 | 2003-03-13 | Celtor Biosystems | Methods and devices for detecting cell-cell interactions |
WO2003020886A3 (en) * | 2001-08-29 | 2004-03-11 | Celtor Biosystems | Methods and devices for detecting cell-cell interactions |
US20040028559A1 (en) * | 2001-11-06 | 2004-02-12 | Peter Schuck | Sample delivery system with laminar mixing for microvolume biosensing |
US20030124623A1 (en) * | 2001-12-05 | 2003-07-03 | Paul Yager | Microfluidic device and surface decoration process for solid phase affinity binding assays |
US7258837B2 (en) | 2001-12-05 | 2007-08-21 | University Of Washington | Microfluidic device and surface decoration process for solid phase affinity binding assays |
US20050266478A1 (en) * | 2002-01-24 | 2005-12-01 | Mingxian Huang | Biochips including ion transport detecting structures and methods of use |
US20040146849A1 (en) * | 2002-01-24 | 2004-07-29 | Mingxian Huang | Biochips including ion transport detecting structures and methods of use |
US7723029B2 (en) | 2002-01-24 | 2010-05-25 | Aviva Biosciences Corporation | Biochips including ion transport detecting structures and methods of use |
US20030157586A1 (en) * | 2002-02-21 | 2003-08-21 | Martin Bonde | Device and method for conducting cellular assays using multiple fluid flow |
US20030175944A1 (en) * | 2002-03-18 | 2003-09-18 | Mengsu Yang | Apparatus and methods for on-chip monitoring of cellular reactions |
US7560267B2 (en) * | 2002-03-18 | 2009-07-14 | City University Of Hong Kong | Apparatus and methods for on-chip monitoring of cellular reactions |
US11027278B2 (en) | 2002-04-17 | 2021-06-08 | Cytonome/St, Llc | Methods for controlling fluid flow in a microfluidic system |
US7112444B2 (en) * | 2002-04-24 | 2006-09-26 | Wisconsin Alumni Research Foundation | Method of performing gradient-based assays in a microfluidic device |
US20040063151A1 (en) * | 2002-04-24 | 2004-04-01 | Beebe David J. | Method of performing gradient-based assays in a microfluidic device |
US20030203504A1 (en) * | 2002-04-26 | 2003-10-30 | John Hefti | Diffusion-based system and method for detecting and monitoring activity of biologic and chemical species |
US20080286750A1 (en) * | 2002-05-04 | 2008-11-20 | Aviva Biosciences Corporation | Apparatus including ion transport detecting structures and methods of use |
US20050009004A1 (en) * | 2002-05-04 | 2005-01-13 | Jia Xu | Apparatus including ion transport detecting structures and methods of use |
US20040004716A1 (en) * | 2002-07-05 | 2004-01-08 | Rashid Mavliev | Method and apparatus for detecting individual particles in a flowable sample |
US6710874B2 (en) | 2002-07-05 | 2004-03-23 | Rashid Mavliev | Method and apparatus for detecting individual particles in a flowable sample |
US20050255472A1 (en) * | 2002-07-19 | 2005-11-17 | Kenichi Yamashita | Molecule analyzing method using microchannel |
US8211629B2 (en) | 2002-08-01 | 2012-07-03 | Xy, Llc | Low pressure sperm cell separation system |
US8486618B2 (en) | 2002-08-01 | 2013-07-16 | Xy, Llc | Heterogeneous inseminate system |
US8497063B2 (en) | 2002-08-01 | 2013-07-30 | Xy, Llc | Sex selected equine embryo production system |
US7855078B2 (en) | 2002-08-15 | 2010-12-21 | Xy, Llc | High resolution flow cytometer |
US20060066840A1 (en) * | 2002-08-21 | 2006-03-30 | Fritz Bernard S | Cytometer having telecentric optics |
US20040211077A1 (en) * | 2002-08-21 | 2004-10-28 | Honeywell International Inc. | Method and apparatus for receiving a removable media member |
US7000330B2 (en) | 2002-08-21 | 2006-02-21 | Honeywell International Inc. | Method and apparatus for receiving a removable media member |
US7283223B2 (en) | 2002-08-21 | 2007-10-16 | Honeywell International Inc. | Cytometer having telecentric optics |
US20070236682A9 (en) * | 2002-08-21 | 2007-10-11 | Fritz Bernard S | Cytometer having telecentric optics |
US11230695B2 (en) | 2002-09-13 | 2022-01-25 | Xy, Llc | Sperm cell processing and preservation systems |
US11261424B2 (en) | 2002-09-13 | 2022-03-01 | Xy, Llc | Sperm cell processing systems |
US7802591B2 (en) | 2002-11-14 | 2010-09-28 | Q Chip Limited | Microfluidic device and methods for construction and application |
US20060108012A1 (en) * | 2002-11-14 | 2006-05-25 | Barrow David A | Microfluidic device and methods for construction and application |
US20060076644A1 (en) * | 2002-12-20 | 2006-04-13 | Meyer Neal W | Nanowire filament |
US7294899B2 (en) | 2002-12-20 | 2007-11-13 | Hewlett-Packard Development Company, L.P. | Nanowire Filament |
US6936496B2 (en) | 2002-12-20 | 2005-08-30 | Hewlett-Packard Development Company, L.P. | Nanowire filament |
US7517453B2 (en) * | 2003-03-01 | 2009-04-14 | The Trustees Of Boston University | Microvascular network device |
US20040168982A1 (en) * | 2003-03-01 | 2004-09-02 | Hemanext, L.L.C. | Microvascular network device |
US8828226B2 (en) | 2003-03-01 | 2014-09-09 | The Trustees Of Boston University | System for assessing the efficacy of stored red blood cells using microvascular networks |
US8709825B2 (en) | 2003-03-28 | 2014-04-29 | Inguran, Llc | Flow cytometer method and apparatus |
US9377390B2 (en) | 2003-03-28 | 2016-06-28 | Inguran, Llc | Apparatus, methods and processes for sorting particles and for providing sex-sorted animal sperm |
US7758811B2 (en) | 2003-03-28 | 2010-07-20 | Inguran, Llc | System for analyzing particles using multiple flow cytometry units |
US11718826B2 (en) | 2003-03-28 | 2023-08-08 | Inguran, Llc | System and method for sorting particles |
US7799569B2 (en) | 2003-03-28 | 2010-09-21 | Inguran, Llc | Process for evaluating staining conditions of cells for sorting |
US8664006B2 (en) | 2003-03-28 | 2014-03-04 | Inguran, Llc | Flow cytometer apparatus and method |
US7943384B2 (en) | 2003-03-28 | 2011-05-17 | Inguran Llc | Apparatus and methods for sorting particles |
US8709817B2 (en) | 2003-03-28 | 2014-04-29 | Inguran, Llc | Systems and methods for sorting particles |
US8748183B2 (en) | 2003-03-28 | 2014-06-10 | Inguran, Llc | Method and apparatus for calibrating a flow cytometer |
US11104880B2 (en) | 2003-03-28 | 2021-08-31 | Inguran, Llc | Photo-damage system for sorting particles |
US10100278B2 (en) | 2003-03-28 | 2018-10-16 | Inguran, Llc | Multi-channel system and methods for sorting particles |
US9040304B2 (en) | 2003-03-28 | 2015-05-26 | Inguran, Llc | Multi-channel system and methods for sorting particles |
US7723116B2 (en) | 2003-05-15 | 2010-05-25 | Xy, Inc. | Apparatus, methods and processes for sorting particles and for providing sex-sorted animal sperm |
US20090081771A1 (en) * | 2003-06-06 | 2009-03-26 | Micronics, Inc. | System and method for heating, cooling and heat cycling on microfluidic device |
US7648835B2 (en) | 2003-06-06 | 2010-01-19 | Micronics, Inc. | System and method for heating, cooling and heat cycling on microfluidic device |
US7544506B2 (en) | 2003-06-06 | 2009-06-09 | Micronics, Inc. | System and method for heating, cooling and heat cycling on microfluidic device |
US20050129582A1 (en) * | 2003-06-06 | 2005-06-16 | Micronics, Inc. | System and method for heating, cooling and heat cycling on microfluidic device |
US20040266022A1 (en) * | 2003-06-26 | 2004-12-30 | Narayanan Sundararajan | Hydrodynamic Focusing Devices |
US7381361B2 (en) | 2003-06-26 | 2008-06-03 | Intel Corporation | Fabricating structures in micro-fluidic channels based on hydrodynamic focusing |
US20040265183A1 (en) * | 2003-06-26 | 2004-12-30 | Narayanan Sundararajan | Fabricating structures in micro-fluidic channels based on hydrodynamic focusing |
US7850907B2 (en) | 2003-06-26 | 2010-12-14 | Intel Corporation | Fabricating structures in micro-fluidic channels based on hydrodynamic focusing |
US7115230B2 (en) | 2003-06-26 | 2006-10-03 | Intel Corporation | Hydrodynamic focusing devices |
US7223611B2 (en) | 2003-10-07 | 2007-05-29 | Hewlett-Packard Development Company, L.P. | Fabrication of nanowires |
US20050072967A1 (en) * | 2003-10-07 | 2005-04-07 | Pavel Kornilovich | Fabrication of nanowires |
US7132298B2 (en) | 2003-10-07 | 2006-11-07 | Hewlett-Packard Development Company, L.P. | Fabrication of nano-object array |
WO2005057186A1 (en) * | 2003-12-10 | 2005-06-23 | Biacore Ab | Sample flow positioning method and analytical system using the method |
US20050199076A1 (en) * | 2003-12-10 | 2005-09-15 | Biacore Ab | Sample flow positioning method and analytical system using the method |
US7219528B2 (en) | 2003-12-10 | 2007-05-22 | Biacore Ab | Sample flow positioning method and analytical system using the method |
US7892725B2 (en) | 2004-03-29 | 2011-02-22 | Inguran, Llc | Process for storing a sperm dispersion |
US7838210B2 (en) | 2004-03-29 | 2010-11-23 | Inguran, LLC. | Sperm suspensions for sorting into X or Y chromosome-bearing enriched populations |
US7407738B2 (en) | 2004-04-02 | 2008-08-05 | Pavel Kornilovich | Fabrication and use of superlattice |
US20050221235A1 (en) * | 2004-04-02 | 2005-10-06 | Pavel Kornilovich | Fabrication and use of superlattice |
US7683435B2 (en) | 2004-04-30 | 2010-03-23 | Hewlett-Packard Development Company, L.P. | Misalignment-tolerant multiplexing/demultiplexing architectures |
US7633098B2 (en) | 2004-04-30 | 2009-12-15 | Hewlett-Packard Development Company, L.P. | Field-effect-transistor multiplexing/demultiplexing architectures |
US7247531B2 (en) | 2004-04-30 | 2007-07-24 | Hewlett-Packard Development Company, L.P. | Field-effect-transistor multiplexing/demultiplexing architectures and methods of forming the same |
US20050241959A1 (en) * | 2004-04-30 | 2005-11-03 | Kenneth Ward | Chemical-sensing devices |
US7641856B2 (en) | 2004-05-14 | 2010-01-05 | Honeywell International Inc. | Portable sample analyzer with removable cartridge |
US20070166195A1 (en) * | 2004-05-14 | 2007-07-19 | Honeywell International Inc. | Analyzer system |
US20050255001A1 (en) * | 2004-05-14 | 2005-11-17 | Honeywell International Inc. | Portable sample analyzer with removable cartridge |
US8071051B2 (en) | 2004-05-14 | 2011-12-06 | Honeywell International Inc. | Portable sample analyzer cartridge |
US20050255600A1 (en) * | 2004-05-14 | 2005-11-17 | Honeywell International Inc. | Portable sample analyzer cartridge |
US8828320B2 (en) | 2004-05-14 | 2014-09-09 | Honeywell International Inc. | Portable sample analyzer cartridge |
US8323564B2 (en) | 2004-05-14 | 2012-12-04 | Honeywell International Inc. | Portable sample analyzer system |
US8540946B2 (en) | 2004-05-14 | 2013-09-24 | Honeywell International Inc. | Portable sample analyzer cartridge |
US8383043B2 (en) | 2004-05-14 | 2013-02-26 | Honeywell International Inc. | Analyzer system |
US20060034685A1 (en) * | 2004-07-07 | 2006-02-16 | Nobuaki Kizuka | Gas turbine and gas turbine cooling method |
US7833147B2 (en) | 2004-07-22 | 2010-11-16 | Inguran, LLC. | Process for enriching a population of sperm cells |
US7760351B2 (en) | 2004-07-27 | 2010-07-20 | Honeywell International Inc. | Cytometer having fluid core stream position control |
US20060023207A1 (en) * | 2004-07-27 | 2006-02-02 | Cox James A | Cytometer having fluid core stream position control |
US7242474B2 (en) | 2004-07-27 | 2007-07-10 | Cox James A | Cytometer having fluid core stream position control |
US20080124805A1 (en) * | 2004-07-27 | 2008-05-29 | Honeywell International Inc. | Cytometer having fluid core stream position control |
US20060024814A1 (en) * | 2004-07-29 | 2006-02-02 | Peters Kevin F | Aptamer-functionalized electrochemical sensors and methods of fabricating and using the same |
US20060051096A1 (en) * | 2004-09-01 | 2006-03-09 | Cox James A | Frequency-multiplexed detection of multiple wavelength light for flow cytometry |
US7612871B2 (en) | 2004-09-01 | 2009-11-03 | Honeywell International Inc | Frequency-multiplexed detection of multiple wavelength light for flow cytometry |
US8329118B2 (en) | 2004-09-02 | 2012-12-11 | Honeywell International Inc. | Method and apparatus for determining one or more operating parameters for a microfluidic circuit |
US20060046300A1 (en) * | 2004-09-02 | 2006-03-02 | Aravind Padmanabhan | Method and apparatus for determining one or more operating parameters for a microfluidic circuit |
US20060166375A1 (en) * | 2004-09-23 | 2006-07-27 | University Of Washington | Microscale diffusion immunoassay utilizing multivalent reactants |
US7550267B2 (en) | 2004-09-23 | 2009-06-23 | University Of Washington | Microscale diffusion immunoassay utilizing multivalent reactants |
US7130046B2 (en) | 2004-09-27 | 2006-10-31 | Honeywell International Inc. | Data frame selection for cytometer analysis |
US20060066852A1 (en) * | 2004-09-27 | 2006-03-30 | Fritz Bernard S | Data frame selection for cytometer analysis |
US7630075B2 (en) | 2004-09-27 | 2009-12-08 | Honeywell International Inc. | Circular polarization illumination based analyzer system |
US20080080306A1 (en) * | 2004-10-11 | 2008-04-03 | Technische Universitat Darmstadt | Microcapillary reactor and method for controlled mixing of nonhomogeneously miscible fluids using said microcapillary reactor |
US20060106557A1 (en) * | 2004-11-18 | 2006-05-18 | Fontaine Norman H | System and method for self-referencing a sensor in a micron-sized deep flow chamber |
US7285420B2 (en) * | 2004-11-18 | 2007-10-23 | Corning Incorporated | System and method for self-referencing a sensor in a micron-sized deep flow chamber |
US8021613B2 (en) | 2004-11-18 | 2011-09-20 | Corning Incorporated | System and method for self-referencing a sensor in a micron-sized deep flow chamber |
US20080063569A1 (en) * | 2004-11-18 | 2008-03-13 | Fontaine Norman H | System and method for self-referencing a sensor in a micron-sized deep flow chamber |
US9260693B2 (en) | 2004-12-03 | 2016-02-16 | Cytonome/St, Llc | Actuation of parallel microfluidic arrays |
US10994273B2 (en) | 2004-12-03 | 2021-05-04 | Cytonome/St, Llc | Actuation of parallel microfluidic arrays |
US10794913B2 (en) | 2004-12-03 | 2020-10-06 | Cytonome/St, Llc | Unitary cartridge for particle processing |
US9823252B2 (en) | 2004-12-03 | 2017-11-21 | Cytonome/St, Llc | Unitary cartridge for particle processing |
US10222378B2 (en) | 2004-12-03 | 2019-03-05 | Cytonome/St, Llc | Unitary cartridge for particle processing |
US10065188B2 (en) | 2004-12-03 | 2018-09-04 | Cytonome/St, Llc | Actuation of parallel microfluidic arrays |
US7405054B1 (en) | 2004-12-13 | 2008-07-29 | University Of Washington Uw Tech Transfer - Invention Licensing | Signal amplification method for surface plasmon resonance-based chemical detection |
US20060138079A1 (en) * | 2004-12-27 | 2006-06-29 | Potyrailo Radislav A | Fabrication process of microfluidic devices |
US20060194420A1 (en) * | 2005-02-28 | 2006-08-31 | Pavel Kornilovich | Multilayer film |
US20090126977A1 (en) * | 2005-02-28 | 2009-05-21 | Paval Kornilovich | Multilayer film |
US7375012B2 (en) | 2005-02-28 | 2008-05-20 | Pavel Kornilovich | Method of forming multilayer film |
US7847368B2 (en) | 2005-02-28 | 2010-12-07 | Hewlett-Packard Development Company, L.P. | Multilayer film with stack of nanometer-scale thicknesses |
US20060244964A1 (en) * | 2005-04-29 | 2006-11-02 | Honeywell International Inc. | Particle parameter determination system |
US7688427B2 (en) | 2005-04-29 | 2010-03-30 | Honeywell International Inc. | Particle parameter determination system |
US20060263256A1 (en) * | 2005-05-17 | 2006-11-23 | Nitrex Metal Inc. | Apparatus and method for controlling atmospheres in heat treating of metals |
US8361410B2 (en) | 2005-07-01 | 2013-01-29 | Honeywell International Inc. | Flow metered analyzer |
US8034296B2 (en) | 2005-07-01 | 2011-10-11 | Honeywell International Inc. | Microfluidic card for RBC analysis |
US8273294B2 (en) | 2005-07-01 | 2012-09-25 | Honeywell International Inc. | Molded cartridge with 3-D hydrodynamic focusing |
WO2007021820A3 (en) * | 2005-08-11 | 2009-04-23 | Eksigent Technologies Llc | Methods for measuring biochemical reactions |
US20090268548A1 (en) * | 2005-08-11 | 2009-10-29 | Eksigent Technologies, Llc | Microfluidic systems, devices and methods for reducing diffusion and compliance effects at a fluid mixing region |
US20090142846A1 (en) * | 2005-08-11 | 2009-06-04 | Eksigent Technologies, Llc | Methods for measuring biochemical reactions |
US20090053814A1 (en) * | 2005-08-11 | 2009-02-26 | Eksigent Technologies, Llc | Microfluidic apparatus and method for sample preparation and analysis |
US20090139576A1 (en) * | 2005-08-11 | 2009-06-04 | Eksigent Technologies, Llc | Microfluidic systems, devices and methods for reducing noise generated by mechanical instabilities |
US7843563B2 (en) | 2005-08-16 | 2010-11-30 | Honeywell International Inc. | Light scattering and imaging optical system |
US20070041013A1 (en) * | 2005-08-16 | 2007-02-22 | Honeywell International Inc. | A light scattering and imaging optical system |
US8340944B2 (en) | 2005-11-30 | 2012-12-25 | The Invention Science Fund I, Llc | Computational and/or control systems and methods related to nutraceutical agent selection and dosing |
US7955836B2 (en) | 2005-11-30 | 2011-06-07 | Micronics, Inc. | Microfluidic mixing and analytical apparatus |
US9468894B2 (en) | 2005-11-30 | 2016-10-18 | Micronics, Inc. | Microfluidic mixing and analytical apparatus |
US20100167384A1 (en) * | 2005-11-30 | 2010-07-01 | Micronics, Inc, | Microfluidic mixing and analytical apparatus |
US10296720B2 (en) | 2005-11-30 | 2019-05-21 | Gearbox Llc | Computational systems and methods related to nutraceuticals |
US7827042B2 (en) | 2005-11-30 | 2010-11-02 | The Invention Science Fund I, Inc | Methods and systems related to transmission of nutraceutical associated information |
US9056291B2 (en) | 2005-11-30 | 2015-06-16 | Micronics, Inc. | Microfluidic reactor system |
US8068991B2 (en) | 2005-11-30 | 2011-11-29 | The Invention Science Fund I, Llc | Systems and methods for transmitting pathogen related information and responding |
US8000981B2 (en) | 2005-11-30 | 2011-08-16 | The Invention Science Fund I, Llc | Methods and systems related to receiving nutraceutical associated information |
US7974856B2 (en) | 2005-11-30 | 2011-07-05 | The Invention Science Fund I, Llc | Computational systems and methods related to nutraceuticals |
US20090148847A1 (en) * | 2006-03-15 | 2009-06-11 | Micronics, Inc. | Rapid magnetic flow assays |
US8222023B2 (en) | 2006-03-15 | 2012-07-17 | Micronics, Inc. | Integrated nucleic acid assays |
US8772017B2 (en) | 2006-03-15 | 2014-07-08 | Micronics, Inc. | Integrated nucleic acid assays |
US8297028B2 (en) | 2006-06-14 | 2012-10-30 | The Invention Science Fund I, Llc | Individualized pharmaceutical selection and packaging |
US20080202931A1 (en) * | 2006-06-15 | 2008-08-28 | Dimiter Nikolov Petsev | Ion Specific Control of the Transport of Fluid and Current in Fluidic Nanochannels |
US7927787B2 (en) | 2006-06-28 | 2011-04-19 | The Invention Science Fund I, Llc | Methods and systems for analysis of nutraceutical associated components |
US20090325276A1 (en) * | 2006-09-27 | 2009-12-31 | Micronics, Inc. | Integrated microfluidic assay devices and methods |
US8101403B2 (en) | 2006-10-04 | 2012-01-24 | University Of Washington | Method and device for rapid parallel microfluidic molecular affinity assays |
US20100081216A1 (en) * | 2006-10-04 | 2010-04-01 | Univeristy Of Washington | Method and device for rapid parallel microfluidic molecular affinity assays |
US9138743B2 (en) | 2006-10-04 | 2015-09-22 | University Of Washington | Method and device for rapid parallel microfluidic molecular affinity assays |
FR2907228A1 (en) * | 2006-10-13 | 2008-04-18 | Rhodia Recherches & Tech | FLUID FLOW DEVICE, ASSEMBLY FOR DETERMINING AT LEAST ONE CHARACTERISTIC OF A PHYSICO-CHEMICAL SYSTEM COMPRISING SUCH A DEVICE, DETERMINING METHOD AND CORRESPONDING SCREENING METHOD |
US8420397B2 (en) | 2006-10-13 | 2013-04-16 | Rhodia Operations | Fluid flow device and assembly employing a temperature gadient for determining at least one characteristic of a physico-chemical system therewith |
WO2008046989A1 (en) * | 2006-10-13 | 2008-04-24 | Rhodia Operations | Fluid flow device, assembly for determining at least one characteristic of a physicochemical system comprising such a device, corresponding determination process and screening process |
US20110032513A1 (en) * | 2006-10-13 | 2011-02-10 | Mathieu Joanicot | Fluid flow device, assembly for determining at least one characteristic of a physico-chemical system therewith |
US20080181821A1 (en) * | 2007-01-29 | 2008-07-31 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Microfluidic chips for allergen detection |
US8617903B2 (en) | 2007-01-29 | 2013-12-31 | The Invention Science Fund I, Llc | Methods for allergen detection |
US10001496B2 (en) | 2007-01-29 | 2018-06-19 | Gearbox, Llc | Systems for allergen detection |
WO2008110147A1 (en) * | 2007-03-09 | 2008-09-18 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Flow channel system and method for connecting analytes to ligands |
US20080299695A1 (en) * | 2007-03-15 | 2008-12-04 | Dalsa Semiconductor Inc. | MICROCHANNELS FOR BioMEMS DEVICES |
EP1970346A2 (en) | 2007-03-15 | 2008-09-17 | DALSA Semiconductor Inc. | Microchannels for biomens devices |
US7799656B2 (en) | 2007-03-15 | 2010-09-21 | Dalsa Semiconductor Inc. | Microchannels for BioMEMS devices |
US20080241000A1 (en) * | 2007-03-27 | 2008-10-02 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Systems for pathogen detection |
EP1982768A2 (en) | 2007-03-27 | 2008-10-22 | Searete LLC | Methods for pathogen detection |
US9029158B2 (en) | 2007-04-06 | 2015-05-12 | California Institute Of Technology | Microfluidic device |
US20090042241A1 (en) * | 2007-04-06 | 2009-02-12 | California Institute Of Technology | Microfluidic device |
US9535059B2 (en) | 2007-04-06 | 2017-01-03 | California Institute Of Technology | Microfluidic device |
US9234884B2 (en) | 2007-04-06 | 2016-01-12 | California Institute Of Technology | Microfluidic device |
US9757729B2 (en) | 2007-04-06 | 2017-09-12 | California Institute Of Technology | Microfluidic device |
US8807879B2 (en) | 2007-04-16 | 2014-08-19 | The General Hospital Corporation | Systems and methods for particle focusing in microchannels |
US11498071B2 (en) | 2007-04-16 | 2022-11-15 | The General Hospital Corporation | Systems and methods for particle focusing in microchannels |
US10549278B2 (en) | 2007-04-16 | 2020-02-04 | The General Hospital Corporation | Systems and methods for particle focusing in microchannels |
US9347595B2 (en) | 2007-04-16 | 2016-05-24 | The General Hospital Corporation | Systems and methods for particle focusing in microchannels |
US8784012B2 (en) * | 2007-04-16 | 2014-07-22 | The General Hospital Corporation | Systems and methods for particle focusing in microchannels |
US9808803B2 (en) | 2007-04-16 | 2017-11-07 | The General Hospital Corporation | Systems and methods for particle focusing in microchannels |
US10688458B2 (en) | 2007-06-21 | 2020-06-23 | Gen-Probe Incorporated | System and method of using multi-chambered receptacles |
US8735055B2 (en) | 2007-06-21 | 2014-05-27 | Gen-Probe Incorporated | Methods of concentrating an analyte |
US11235295B2 (en) | 2007-06-21 | 2022-02-01 | Gen-Probe Incorporated | System and method of using multi-chambered receptacles |
US7780336B2 (en) | 2007-06-21 | 2010-08-24 | Gen-Probe Incorporated | Instruments and methods for mixing the contents of a detection chamber |
US9744506B2 (en) | 2007-06-21 | 2017-08-29 | Gen-Probe Incorporated | Instruments for mixing the contents of a detection chamber |
US8765367B2 (en) | 2007-06-21 | 2014-07-01 | Gen-Probe Incorporated | Methods and instruments for processing a sample in a multi-chambered receptacle |
US8480976B2 (en) | 2007-06-21 | 2013-07-09 | Gen-Probe Incorporated | Instruments and methods for mixing the contents of a detection chamber |
US8491178B2 (en) | 2007-06-21 | 2013-07-23 | Gen-Probe Incorporated | Instruments and methods for mixing the contents of a detection chamber |
US10744469B2 (en) | 2007-06-21 | 2020-08-18 | Gen-Probe Incorporated | Multi-chambered receptacles |
US8052929B2 (en) | 2007-06-21 | 2011-11-08 | Gen-Probe Incorporated | Gravity-assisted mixing methods |
US8784745B2 (en) | 2007-06-21 | 2014-07-22 | Gen-Probe Incorporated | Methods for manipulating liquid substances in multi-chambered receptacles |
US11235294B2 (en) | 2007-06-21 | 2022-02-01 | Gen-Probe Incorporated | System and method of using multi-chambered receptacles |
US8828654B2 (en) | 2007-06-21 | 2014-09-09 | Gen-Probe Incorporated | Methods for manipulating liquid substances in multi-chambered receptacles |
US7767447B2 (en) | 2007-06-21 | 2010-08-03 | Gen-Probe Incorporated | Instruments and methods for exposing a receptacle to multiple thermal zones |
US8048375B2 (en) | 2007-06-21 | 2011-11-01 | Gen-Probe Incorporated | Gravity-assisted mixing methods |
US20090068760A1 (en) * | 2007-09-11 | 2009-03-12 | University Of Washington | Microfluidic assay system with dispersion monitoring |
US7736891B2 (en) | 2007-09-11 | 2010-06-15 | University Of Washington | Microfluidic assay system with dispersion monitoring |
US20090086249A1 (en) * | 2007-10-01 | 2009-04-02 | Brother Kogyo Kabushiki Kaisha | Image formation device and computer-readable record medium |
US9132398B2 (en) | 2007-10-12 | 2015-09-15 | Rheonix, Inc. | Integrated microfluidic device and methods |
US20100231910A1 (en) * | 2008-07-08 | 2010-09-16 | Rashid Mavliev | Systems and methods for in-line monitoring of particles in opagque flows |
US20100007879A1 (en) * | 2008-07-08 | 2010-01-14 | Rashid Mavliev | Systems and methods for in-line monitoring of particles in opaque flows |
US7738101B2 (en) | 2008-07-08 | 2010-06-15 | Rashid Mavliev | Systems and methods for in-line monitoring of particles in opaque flows |
US8359484B2 (en) | 2008-09-18 | 2013-01-22 | Honeywell International Inc. | Apparatus and method for operating a computing platform without a battery pack |
US10107797B2 (en) | 2008-10-03 | 2018-10-23 | Micronics, Inc. | Microfluidic apparatus and methods for performing blood typing and crossmatching |
EP2204348A2 (en) | 2009-01-05 | 2010-07-07 | DALSA Semiconductor Inc. | Method of making bio MEMS devices |
US20100279393A1 (en) * | 2009-02-05 | 2010-11-04 | Taisuke Hirono | Micro chip device |
US9649631B2 (en) | 2009-06-04 | 2017-05-16 | Leidos Innovations Technology, Inc. | Multiple-sample microfluidic chip for DNA analysis |
US9656261B2 (en) | 2009-06-04 | 2017-05-23 | Leidos Innovations Technology, Inc. | DNA analyzer |
US9067207B2 (en) | 2009-06-04 | 2015-06-30 | University Of Virginia Patent Foundation | Optical approach for microfluidic DNA electrophoresis detection |
US10603417B2 (en) | 2009-10-12 | 2020-03-31 | Hemanext Inc. | System for extended storage of red blood cells and methods of use |
US9844615B2 (en) | 2009-10-12 | 2017-12-19 | New Health Sciences, Inc. | System for extended storage of red blood cells and methods of use |
US11433164B2 (en) | 2009-10-12 | 2022-09-06 | Hemanext Inc. | System for extended storage of red blood cells and methods of use |
US8569052B2 (en) | 2009-10-12 | 2013-10-29 | New Health Sciences, Inc. | Oxygen depletion devices and methods for removing oxygen from red blood cells |
US9296990B2 (en) | 2009-10-12 | 2016-03-29 | New Health Sciences, Inc. | Oxygen depletion devices and methods for removing oxygen from red blood cells |
US8535421B2 (en) | 2009-10-12 | 2013-09-17 | New Health Sciences, Inc. | Blood storage bag system and depletion devices with oxygen and carbon dioxide depletion capabilities |
US9199016B2 (en) | 2009-10-12 | 2015-12-01 | New Health Sciences, Inc. | System for extended storage of red blood cells and methods of use |
US9095662B2 (en) | 2009-10-12 | 2015-08-04 | New Health Sciences, Inc. | Blood storage bag system and depletion devices with oxygen and carbon dioxide depletion capabilities |
US9895692B2 (en) | 2010-01-29 | 2018-02-20 | Micronics, Inc. | Sample-to-answer microfluidic cartridge |
US20130011928A1 (en) * | 2010-03-29 | 2013-01-10 | Analogic Corporation | Optical detection system and/or method |
US10136635B2 (en) | 2010-05-05 | 2018-11-27 | New Health Sciences, Inc. | Irradiation of red blood cells and anaerobic storage |
US11284616B2 (en) | 2010-05-05 | 2022-03-29 | Hemanext Inc. | Irradiation of red blood cells and anaerobic storage |
US9539375B2 (en) | 2010-05-05 | 2017-01-10 | New Health Sciences, Inc. | Integrated leukocyte, oxygen and/or CO2 depletion, and plasma separation filter device |
US10065134B2 (en) | 2010-05-05 | 2018-09-04 | New Health Sciences, Inc. | Integrated leukocyte, oxygen and/or CO2 depletion, and plasma separation filter device |
US9005343B2 (en) | 2010-05-05 | 2015-04-14 | New Health Sciences, Inc. | Integrated leukocyte, oxygen and/or CO2 depletion, and plasma separation filter device |
US9182353B2 (en) | 2010-07-22 | 2015-11-10 | Hach Company | Lab-on-a-chip for alkalinity analysis |
US10251387B2 (en) | 2010-08-25 | 2019-04-09 | New Health Sciences, Inc. | Method for enhancing red blood cell quality and survival during storage |
US9339025B2 (en) | 2010-08-25 | 2016-05-17 | New Health Sciences, Inc. | Method for enhancing red blood cell quality and survival during storage |
US8961764B2 (en) | 2010-10-15 | 2015-02-24 | Lockheed Martin Corporation | Micro fluidic optic design |
US9180452B2 (en) | 2011-02-18 | 2015-11-10 | Koninklijke Philips N.V. | Microfluidic resistance network and microfluidic device |
EP2490005A1 (en) * | 2011-02-18 | 2012-08-22 | Koninklijke Philips Electronics N.V. | Microfluidic resistance network and microfluidic device |
WO2012110943A1 (en) * | 2011-02-18 | 2012-08-23 | Koninklijke Philips Electronics N.V. | Microfluidic resistance network and microfluidic device |
RU2599657C2 (en) * | 2011-02-18 | 2016-10-10 | Конинклейке Филипс Н.В. | Microfluidic resistant network and microfluidic device |
US9067004B2 (en) | 2011-03-28 | 2015-06-30 | New Health Sciences, Inc. | Method and system for removing oxygen and carbon dioxide during red cell blood processing using an inert carrier gas and manifold assembly |
US9968718B2 (en) | 2011-03-28 | 2018-05-15 | New Health Sciences, Inc. | Method and system for removing oxygen and carbon dioxide during red cell blood processing using an inert carrier gas and manifold assembly |
US8663583B2 (en) | 2011-12-27 | 2014-03-04 | Honeywell International Inc. | Disposable cartridge for fluid analysis |
US8980635B2 (en) | 2011-12-27 | 2015-03-17 | Honeywell International Inc. | Disposable cartridge for fluid analysis |
US8741233B2 (en) | 2011-12-27 | 2014-06-03 | Honeywell International Inc. | Disposable cartridge for fluid analysis |
US8741235B2 (en) | 2011-12-27 | 2014-06-03 | Honeywell International Inc. | Two step sample loading of a fluid analysis cartridge |
US8741234B2 (en) | 2011-12-27 | 2014-06-03 | Honeywell International Inc. | Disposable cartridge for fluid analysis |
US9322054B2 (en) | 2012-02-22 | 2016-04-26 | Lockheed Martin Corporation | Microfluidic cartridge |
US9988676B2 (en) | 2012-02-22 | 2018-06-05 | Leidos Innovations Technology, Inc. | Microfluidic cartridge |
US9977037B2 (en) | 2012-05-22 | 2018-05-22 | New Health Sciences, Inc. | Capillary network devices and methods of use |
US9180449B2 (en) | 2012-06-12 | 2015-11-10 | Hach Company | Mobile water analysis |
USD900330S1 (en) | 2012-10-24 | 2020-10-27 | Genmark Diagnostics, Inc. | Instrument |
US9957553B2 (en) | 2012-10-24 | 2018-05-01 | Genmark Diagnostics, Inc. | Integrated multiplex target analysis |
US11952618B2 (en) | 2012-10-24 | 2024-04-09 | Roche Molecular Systems, Inc. | Integrated multiplex target analysis |
US10495656B2 (en) | 2012-10-24 | 2019-12-03 | Genmark Diagnostics, Inc. | Integrated multiplex target analysis |
USD768872S1 (en) | 2012-12-12 | 2016-10-11 | Hach Company | Cuvette for a water analysis instrument |
US8945913B2 (en) | 2012-12-17 | 2015-02-03 | Leukodx Ltd. | Kits, compositions and methods for detecting a biological condition |
US11703506B2 (en) | 2012-12-17 | 2023-07-18 | Accellix Ltd. | Systems and methods for determining a chemical state |
US10761094B2 (en) | 2012-12-17 | 2020-09-01 | Accellix Ltd. | Systems and methods for determining a chemical state |
US9989523B2 (en) | 2012-12-17 | 2018-06-05 | Leukodx Ltd. | Kits, compositions and methods for detecting a biological condition |
US10610861B2 (en) | 2012-12-17 | 2020-04-07 | Accellix Ltd. | Systems, compositions and methods for detecting a biological condition |
US9207239B2 (en) | 2012-12-17 | 2015-12-08 | Leukodx Ltd. | Kits, compositions and methods for detecting a biological condition |
US10065186B2 (en) | 2012-12-21 | 2018-09-04 | Micronics, Inc. | Fluidic circuits and related manufacturing methods |
US11181105B2 (en) | 2012-12-21 | 2021-11-23 | Perkinelmer Health Sciences, Inc. | Low elasticity films for microfluidic use |
US10518262B2 (en) | 2012-12-21 | 2019-12-31 | Perkinelmer Health Sciences, Inc. | Low elasticity films for microfluidic use |
US10436713B2 (en) | 2012-12-21 | 2019-10-08 | Micronics, Inc. | Portable fluorescence detection system and microassay cartridge |
US9877476B2 (en) | 2013-02-28 | 2018-01-30 | New Health Sciences, Inc. | Gas depletion and gas addition devices for blood treatment |
US10687526B2 (en) | 2013-02-28 | 2020-06-23 | Hemanext Inc. | Gas depletion and gas addition devices for blood treatment |
US9410663B2 (en) | 2013-03-15 | 2016-08-09 | Genmark Diagnostics, Inc. | Apparatus and methods for manipulating deformable fluid vessels |
US10391489B2 (en) | 2013-03-15 | 2019-08-27 | Genmark Diagnostics, Inc. | Apparatus and methods for manipulating deformable fluid vessels |
US9453613B2 (en) | 2013-03-15 | 2016-09-27 | Genmark Diagnostics, Inc. | Apparatus, devices, and methods for manipulating deformable fluid vessels |
US10807090B2 (en) | 2013-03-15 | 2020-10-20 | Genmark Diagnostics, Inc. | Apparatus, devices, and methods for manipulating deformable fluid vessels |
US9222623B2 (en) | 2013-03-15 | 2015-12-29 | Genmark Diagnostics, Inc. | Devices and methods for manipulating deformable fluid vessels |
US11016108B2 (en) | 2013-05-07 | 2021-05-25 | Perkinelmer Health Sciences, Inc. | Microfluidic devices and methods for performing serum separation and blood cross-matching |
US10087440B2 (en) | 2013-05-07 | 2018-10-02 | Micronics, Inc. | Device for preparation and analysis of nucleic acids |
US10190153B2 (en) | 2013-05-07 | 2019-01-29 | Micronics, Inc. | Methods for preparation of nucleic acid-containing samples using clay minerals and alkaline solutions |
US10386377B2 (en) | 2013-05-07 | 2019-08-20 | Micronics, Inc. | Microfluidic devices and methods for performing serum separation and blood cross-matching |
US20160137963A1 (en) * | 2013-06-28 | 2016-05-19 | Danmarks Tekniske Universitet | A Microfluidic Device with a Diffusion Barrier |
USD881409S1 (en) | 2013-10-24 | 2020-04-14 | Genmark Diagnostics, Inc. | Biochip cartridge |
US11029315B2 (en) | 2013-11-14 | 2021-06-08 | Cambridge Enterprise Limited | Fluidic separation and detection |
US11959923B2 (en) | 2013-11-14 | 2024-04-16 | Cambridge Enterprise Limited | Fluidic separation and detection |
US10295545B2 (en) | 2013-11-14 | 2019-05-21 | Cambridge Enterprise Limited | Fluidic separation and detection |
US11105730B2 (en) | 2014-04-09 | 2021-08-31 | Nch Corporation | System and method for detecting biofilm growth in water systems |
US10005080B2 (en) | 2014-11-11 | 2018-06-26 | Genmark Diagnostics, Inc. | Instrument and cartridge for performing assays in a closed sample preparation and reaction system employing electrowetting fluid manipulation |
US9498778B2 (en) | 2014-11-11 | 2016-11-22 | Genmark Diagnostics, Inc. | Instrument for processing cartridge for performing assays in a closed sample preparation and reaction system |
US9598722B2 (en) | 2014-11-11 | 2017-03-21 | Genmark Diagnostics, Inc. | Cartridge for performing assays in a closed sample preparation and reaction system |
US10864522B2 (en) | 2014-11-11 | 2020-12-15 | Genmark Diagnostics, Inc. | Processing cartridge and method for detecting a pathogen in a sample |
DE102015204235B4 (en) * | 2015-03-10 | 2016-12-15 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Fluidic structure with holding section and method for uniting two fluid volumes |
DE102015204235A1 (en) * | 2015-03-10 | 2016-09-15 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Fluidic structure with holding section and method for uniting two fluid volumes |
US10058091B2 (en) | 2015-03-10 | 2018-08-28 | New Health Sciences, Inc. | Oxygen reduction disposable kits, devices and methods of use thereof |
US11638421B2 (en) | 2015-03-10 | 2023-05-02 | Hemanext Inc. | Oxygen reduction disposable kits, devices and methods of use thereof |
US11350626B2 (en) | 2015-03-10 | 2022-06-07 | Hemanext Inc. | Oxygen reduction disposable kits, devices and methods of use thereof (ORDKit) |
US11375709B2 (en) | 2015-03-10 | 2022-07-05 | Hemanext Inc. | Oxygen reduction disposable kits, devices and methods of use thereof |
US10849824B2 (en) | 2015-04-23 | 2020-12-01 | Hemanext Inc. | Anaerobic blood storage containers |
US9801784B2 (en) | 2015-04-23 | 2017-10-31 | New Health Sciences, Inc. | Anaerobic blood storage containers |
US11013771B2 (en) | 2015-05-18 | 2021-05-25 | Hemanext Inc. | Methods for the storage of whole blood, and compositions thereof |
US11633737B2 (en) * | 2016-04-20 | 2023-04-25 | Cellix Limited | Microfluidic chip for focussing a stream of particulate containing fluid |
US11147876B2 (en) | 2016-05-27 | 2021-10-19 | Hemanext Inc. | Anaerobic blood storage and pathogen inactivation method |
US11911471B2 (en) | 2016-05-27 | 2024-02-27 | Hemanext Inc. | Anaerobic blood storage and pathogen inactivation method |
US10583192B2 (en) | 2016-05-27 | 2020-03-10 | New Health Sciences, Inc. | Anaerobic blood storage and pathogen inactivation method |
WO2021180289A1 (en) | 2020-03-11 | 2021-09-16 | Fida Biosystems Aps | A method, an apparatus, an assembly and a system suitable for determining a characteristic property of a molecular interaction |
WO2022147191A1 (en) * | 2020-12-31 | 2022-07-07 | Intuitive Surgical Operations, Inc. | Fluorescence evaluation apparatuses, systems, and methods |
Also Published As
Publication number | Publication date |
---|---|
JP2001504936A (en) | 2001-04-10 |
DE69724943T2 (en) | 2004-07-15 |
DE69724943D1 (en) | 2003-10-23 |
EP0890094B1 (en) | 2003-09-17 |
EP0890094A4 (en) | 1999-10-06 |
AU3877797A (en) | 1997-11-07 |
US5716852A (en) | 1998-02-10 |
WO1997039338A1 (en) | 1997-10-23 |
JP2007292773A (en) | 2007-11-08 |
EP0890094A1 (en) | 1999-01-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5972710A (en) | Microfabricated diffusion-based chemical sensor | |
US20060073599A1 (en) | Microfabricated diffusion-based chemical sensor | |
WO1997039338A9 (en) | Microfabricated diffusion-based chemical sensor | |
US5948684A (en) | Simultaneous analyte determination and reference balancing in reference T-sensor devices | |
US6277641B1 (en) | Methods for analyzing the presence and concentration of multiple analytes using a diffusion-based chemical sensor | |
US6136272A (en) | Device for rapidly joining and splitting fluid layers | |
US6541213B1 (en) | Microscale diffusion immunoassay | |
US6297061B1 (en) | Simultaneous particle separation and chemical reaction | |
US7011791B2 (en) | Microfluidic devices for rotational manipulation of the fluidic interface between multiple flow streams | |
US20030124623A1 (en) | Microfluidic device and surface decoration process for solid phase affinity binding assays | |
Weigl et al. | Silicon-microfabricated diffusion-based optical chemical sensor | |
US20020090644A1 (en) | Microscale diffusion immunoassay |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: WASHINGTON, UNIVERSITY OF, WASHINGTON Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:WEIGL, BERNHARD H.;YAGER, PAUL;BRODY, JAMES P.;AND OTHERS;REEL/FRAME:009712/0786;SIGNING DATES FROM 19981029 TO 19981210 |
|
STCF | Information on status: patent grant |
Free format text: PATENTED CASE |
|
CC | Certificate of correction | ||
FEPP | Fee payment procedure |
Free format text: PAYER NUMBER DE-ASSIGNED (ORIGINAL EVENT CODE: RMPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY Free format text: PAT HOLDER CLAIMS SMALL ENTITY STATUS, ENTITY STATUS SET TO SMALL (ORIGINAL EVENT CODE: LTOS); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY |
|
REFU | Refund |
Free format text: REFUND - PAYMENT OF MAINTENANCE FEE, 4TH YEAR, LARGE ENTITY (ORIGINAL EVENT CODE: R1551); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY |
|
FPAY | Fee payment |
Year of fee payment: 4 |
|
FEPP | Fee payment procedure |
Free format text: PAYER NUMBER DE-ASSIGNED (ORIGINAL EVENT CODE: RMPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY |
|
FPAY | Fee payment |
Year of fee payment: 8 |
|
FEPP | Fee payment procedure |
Free format text: PAT HOLDER NO LONGER CLAIMS SMALL ENTITY STATUS, ENTITY STATUS SET TO UNDISCOUNTED (ORIGINAL EVENT CODE: STOL); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY |
|
REMI | Maintenance fee reminder mailed | ||
FPAY | Fee payment |
Year of fee payment: 12 |
|
SULP | Surcharge for late payment |
Year of fee payment: 11 |